Adult-onset Growth Hormone Deficiency Research Articles

IGF-1 as screening tool for acromegaly and adult-onset growth hormone deficiency in the Netherlands.

Insulin-like growth factor 1 (IGF-1) measurements play a central role in the diagnosis and follow-up of acromegaly and growth hormone deficiency. However, improving health care outcomes for these patients involves an intricate process of laboratory diagnostics and skilled health care professionals. The integrated effects of IGF-1 reports on diagnosis and treatment decisions are yet unknown. Extended quality assessment, distributing the description of five (real) patient cases with accompanying blood samples. Patients suspected or during follow up for acromegaly or adult onset of growth hormone deficiency were included. Laboratory specialists and endocrinologists in the same centre were asked to interpret their centre-specific IGF-1 results by using a laboratory and medical questionnaire. This way, insight could be obtained into the combined effects of different assays, assay harmonisation, reference value sets, and individual physician interpretation in relation to guidelines, thus reviewing the entire diagnostic and management process. Limited variation (CV 13.8 ± 2.8) was found in IGF-1 concentrations despite different use of the harmonization sample and factor among laboratories. This interlaboratory variation increased upon conversion to SD scores (CV 15.7 ± 40.7) as a consequence of the use of different reference value sets. Furthermore, there was a lack of adherence to international guidelines among endocrinologists. Highly variable diagnostic and treatment outcomes in acromegaly and AGHD in the Netherlands can be attributed to increased variability of IGF-1 upon conversion to SD scores and low adherence to clinical guidelines.

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.

Effects of 18 months of GH replacement on cardiovascular risk factors and quality of life in GH deficient adults; a randomized controlled trial using a fixed very low and a standard dose of GH

ObjectiveLittle is known of the effects of a fixed very low dose of growth hormone (GH) replacement on cardiovascular risk factors, bone mass, muscle strength and quality of life (QoL) in hypopituitary patients. Design/patients/methodsThis was an open-label randomized study performed at a single center. Consecutive hypopituitary patients with adult onset GH deficiency (GHD) and BMI ≥ 27 kg/m2 were randomized to receive a very low fixed dose of GH (LG, n = 9) or a standard dose of GH (SG, n = 9). Body composition, glucose and lipid metabolism, bone mineral content (BMC) and density (BMD), muscle strength, and QoL were measured at baseline and after 6, 12 and 18 months. ResultsThe fixed GH dose in LG was 0.1 mg/day. In SG, the mean baseline GH dose of 0.13 mg/day was gradually increased to 0.31 mg/day at study end. Lean body mass (LBM) as measured using DEXA as well as total body water (TBW) and extracellular water (ECW) were increased only in SG (P < 0.01, P < 0.05, and P < 0.01 vs. LG, respectively). There were no between-groups differences in BMD, BMC, insulin sensitivity, lipids, or muscle strength. Finally, although not significant compared with SG, a sustained improvement in QoL was seen in LG according to the QoL-AGHDA questionnaire. ConclusionIn this pilot study, a fixed very low GH dose improved QoL in GHD adults without any induction of fluid retention. Other effects were comparable to those produced by the standard GH dose. Replacement with a very low GH dose could therefore be a treatment option in hypopituitary patients, especially in patients who do not tolerate higher GH dosage.Trial registrationThis study is registered at ClinicalTrials.gov, EU-nr 2009–016783-37.

MRI intensity and pituitary volume predict adult-onset growth hormone deficiency in patients with obesity and overweight: a new potential tool guiding subsequent diagnostic testing

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

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.

A 17-year-old boy with lymphocytic infundibuloneurohypophysitis who developed non-alcoholic steatohepatitis effectively treated with growth hormone.

SummaryWe encountered a case of childhood-onset lymphocytic infundibuloneurohypophysitis, based on the MRI and endocrinological findings, with decreased function of the anterior and posterior lobes of the pituitary. Three years after the diagnosis, the patient developed non-alcoholic steatohepatitis (NASH), which was effectively treated by growth hormone (GH) supplementation. The present case demonstrated that NASH can be effectively treated by short-term GH supplementation, even in late childhood.Learning pointsIn recent years, the efficacy of growth hormone replacement therapy in normalizing the liver function of adult-onset growth hormone deficiency patients with non-alcoholic steatohepatitis (NASH) has been reported.Lymphocytic infundibuloneurohypophysitis is a very rare disease, particularly in childhood.We here presented a rare case of a child with lymphocytic infundibuloneurohypophysitis who developed NASH and showed substantial improvement in liver function after growth hormone treatment.

Abstract 63: A case of adult-onset growth hormone deficiency associated with symptomatic post-prandial hypoglycemia

Abstract 63: A case of adult-onset growth hormone deficiency associated with symptomatic post-prandial hypoglycemia

Safety and effectiveness of replacement with biosimilar growth hormone in adults with growth hormone deficiency: results from an international, post-marketing surveillance study (PATRO Adults)

PurposeTo evaluate safety and effectiveness of biosimilar recombinant human growth hormone (rhGH; Omnitrope®) in adults with growth hormone deficiency (GHD), using data from the PATRO Adults study.MethodsPATRO Adults was a post-marketing surveillance study conducted in hospitals and specialized endocrinology units across Europe. The primary objective was to assess the safety of rhGH in adults treated in routine clinical practice. All adverse events (AEs) were monitored and recorded for the complete duration of Omnitrope® treatment. Effectiveness was evaluated as a secondary objective.ResultsAs of January 2020, 1447 patients (50.9% male) had been enrolled from 82 centers in 9 European countries. Most patients had adult-onset GHD (n = 1179; 81.5%); 721 (49.8%) were rhGH-naïve at study entry. Overall, 1056 patients (73.0%) reported adverse events (AEs; n = 5397 events); the majority were mild-to-moderate in intensity. Treatment-related AEs were reported in 117 patients (8.1%; n = 189 events); the most commonly reported (MedDRA preferred terms) were arthralgia (n = 19), myalgia (n = 16), headache (n = 14), and edema peripheral (n = 10). In total, 495 patients (34.2%) had serious AEs (SAEs; n = 1131 events); these were considered treatment-related in 28 patients (1.9%; n = 35 events). Mean (standard deviation) IGF-I SDS increased from – 2.34 (1.47) at baseline to – 0.23 (1.65) at 12 months, and remained relatively stable thereafter (up to 3 years). Body mass index remained stable between baseline and 3 years.ConclusionData from PATRO Adults indicate biosimilar rhGH (Omnitrope®) is not associated with any unexpected safety signals, and is effective in adults with GHD treated in real-world clinical practice.

Experience of a Pituitary Clinic for US Military Veterans With Traumatic Brain Injury.

Traumatic brain injury (TBI) is considered the "signature" injury of veterans returning from wartime conflicts in Iraq and Afghanistan. While moderate/severe TBI is associated with pituitary dysfunction, this association has not been well established in the military setting and in mild TBI (mTBI). Screening for pituitary dysfunction resulting from TBI in veteran populations is inconsistent across Veterans Affairs (VA) institutions, and such dysfunction often goes unrecognized and untreated. This work aims to report the experience of a pituitary clinic in screening for and diagnosis of pituitary dysfunction. A retrospective analysis was conducted in a US tertiary care center of veterans referred to the VA Puget Sound Healthcare System pituitary clinic with a history of TBI at least 12 months prior. Main outcome measures included demographics, medical history, symptom burden, baseline hormonal evaluation, brain imaging, and provocative testing for adrenal insufficiency (AI) and adult-onset growth hormone deficiency (AGHD). Fatigue, cognitive/memory problems, insomnia, and posttraumatic stress disorder were reported in at least two-thirds of the 58 patients evaluated. Twenty-two (37.9%) were diagnosed with at least one pituitary hormone deficiency, including 13 (22.4%) AI, 12 (20.7%) AGHD, 2 (3.4%) secondary hypogonadism, and 5 (8.6%) hyperprolactinemia diagnoses; there were no cases of thyrotropin deficiency. A high prevalence of chronic AI and AGHD was observed among veterans with TBI. Prospective, larger studies are needed to confirm these results and determine the effects of hormone replacement on long-term outcomes in this setting.

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).

Is Growth Hormone Insufficiency the Missing Link Between Obesity, Male Gender, Age, and COVID‐19 Severity?

Evidence has emerged regarding an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) with worse prognosis in elderly male patients with obesity, and blunted growth hormone (GH) secretion represents a feature of this population subgroup. Here, a comprehensive review of the possible links between GH–insulinlike growth factor 1 axis impairment and coronavirus disease 2019 (COVID‐19) severity is offered. First, unequivocal evidence suggests that immune system dysregulation represents a key element in determining SARS‐CoV‐2 severity, as well as the association with adult‐onset GH deficiency (GHD); notably, if GH is physiologically involved in the development and maintenance of the immune system, its pharmacological replacement in GHD patients seems to positively influence their inflammatory status. In addition, the impaired fibrinolysis associated with GHD may represent a further link between GH–insulin‐like growth factor 1 axis impairment and COVID‐19 severity, as it has been associated with both conditions. In conclusion, several sources of evidence have supported a relationship between GHD and COVID‐19, and they also shed light upon potential beneficial effects of recombinant GH treatment on COVID‐19 patients.

Differences in acquired and idiopathic adult-onset growth hormone deficiency

Differences in acquired and idiopathic adult-onset growth hormone deficiency

Early versus late initiation of GH replacement in adult-onset hypopituitarism.

Introduction:Adult-onset growth hormone deficiency (AGHD) is usually the last deficiency to be substituted in hypopituitarism. In children with documented GH deficiency, treatment without delay is crucial for achieving optimal effects on growth and development. In adults, it is not known whether a delay in treatment initiation influences biochemical response and the favourable physiological effects resulting from GH replacement therapy (GHRT).Methods:A total of 1085 GH-deficient adults from KIMS (Pfizer International Metabolic Database) were included, adequately replaced with all pituitary hormones except for GH at baseline. Patients were stratified by sex and age (20–50 years and ≥50 years) and subsequently divided into two groups below and above the median duration of unsubstituted AGHD for that subgroup. The median time of unsubstituted GHD for the total cohort was 2.53 years (P5 = 0.35, P95 = 24.42).Results:Beneficial effects of 4 years of GHRT were observed on lipids and quality of life in all subgroups. A decrease in waist circumference was observed only in older (>50 years) patients. There was no difference in IGF-I SDS and in GH dose required to normalize IGF-I in patients with a duration of unsubstituted AGHD above or below the median. No relevant differences were found between the groups for anthropometric measures, cardiovascular risk factors and quality of life scores.Conclusion:In contrast to GHD in children and adolescents, no difference could be established in treatment response between early or late initiation of GHRT in AGHD in terms of required GH dose, IGF-I, metabolic health and quality of life.

SUN-310 Growth Hormone Deficiency and Replacement Therapy: Association with Health-Related Physical Fitness

Objective: To compare health-related physical fitness (HRPF) in patients with severe adult growth hormone deficiency (AGHD) according to the deficiency onset phase, and to evaluate the effects of a six-months human growth hormone (rhGH) replacement therapy on HRPF, in a subgroup of patients. Methods: First arm: cross-sectional observational study at baseline of naive rhGH multiple pituitary hormonal deficiency (MPHD) hypopituitarism patients - adult-onset growth hormone deficiency (AO-GHD) versus child onset growth hormone deficiency (CO-GHD). Second arm: a 6-month intervention clinical trial in a selected group of a non-randomized, non-controlled cohort. HRPF was evaluated by measuring isokinetic and isometric torque stensor strength at the knee using an isokinetic dynamometer, handgrip strength and six-minute walk test. Body composition was assessed by DXA. Results: Patients who presented AO-GHD had higher BMI than CO-GHD (28.1±3.5 x 22.4±4.8; p=0.017), but body composition (lean body mass%:57.9±7.9 x 58.9±8.6;p=0.816/fatty body mass%:39.3±6.8 x 36.0±9.1;p=0.434), stensor peak torque/body weight at 60, 90 and 180deg/s (2.18±0.6 x 2.18±0.6; p=0.580/1.99±0.5 x 2.14±0.5;p=0.546/1.52±0.4 x 1.64±0.4;p=0.547), isometric torque/body weight at the knee (2.62±0.7 x 2.91±0.6;p=0.357) and six-minute walk test (570.2±76.0cm x 554.1±91.0cm;p= 0.703) did not differ between groups. Handgrip strength test also showed significant reduction in scores for age and gender in both groups of GHD patients. After six months of rhGH, no improvement in muscular strength tests was found. There was a significant worsening in the six-minute walk test (575.1±84cm x 545.4±90.6cm; p=0.033) despite the improvement in body composition (lean body mass%:59.7±8.6 x 63.6±11.1;p=0.005/fatty body mass%:35.7±9.2 x 32.9±10.0;p=0.003). Conclusion: Despite differences in BMI, there were no other differences in HRPF between AO-GHD and CO-GHD patients. The decrease of the six-minute walking test performance after rhGH replacement therapy supports the clinical evidence that the GH regulates bioenergetics in human skeletal muscle fibers. Although the treatment had a short period, GH might have stimulated the anaerobic and suppressed the aerobic energy system.

MON-265 Once-Weekly Somapacitan in Japanese Adults with GH Deficiency Was Well Tolerated, with Similar Efficacy to Daily GH: A Randomized Trial

Somapacitan is a long-acting, reversible albumin-binding human growth hormone (GH) derivative based on a proven protraction technology. The objective of this trial was to evaluate the safety, efficacy and treatment satisfaction of once-weekly somapacitan compared with daily GH (Norditropin®) over 52 weeks in Japanese patients with adult GH deficiency (AGHD).This was a phase 3, multicenter, randomized, open-label, parallel-group, active-controlled trial (NCT03075644). Patients previously treated with human GH were randomized 1:3 to either daily GH or somapacitan, respectively, to undergo 20 weeks of dose titration and 32 weeks of fixed-dose treatment. The primary endpoint was the incidence of adverse events (AEs) from baseline to week 53. Secondary endpoints included change from baseline in visceral, subcutaneous and total adipose tissue (VAT, SAT and TAT, respectively) assessed with computerized tomography scans; change from baseline in treatment satisfaction evaluated using Treatment Satisfaction Questionnaire for Medication (TSQM-9) scores; and occurrence of anti-somapacitan antibodies.In total, 62 patients were randomized (16 to the daily GH and 46 to the somapacitan treatment arm), of which 60 completed the trial. Baseline characteristics for daily GH vs somapacitan groups, respectively, were: 43.8% vs 47.8% female, 87.5% vs 80.4% adult-onset GH deficiency, mean (SD) age 49.3 (11.5) vs 54.1 (12.1) years, weight 67.9 (12.0) vs 69.4 (22.7) kg, body mass index 24.8 (3.7) vs 26.4 (6.7) kg/m2, and GH dose at screening 0.29 (0.14) vs 0.31 (0.17) mg. Rate of AEs per 100 patient-years was similar between treatment arms (309.8 for daily GH, 312.7 for once-weekly somapacitan); most AEs were mild (97.9% and 93.1%, respectively) and none were severe. Four AEs in the somapacitan arm were serious; all were considered unlikely related to treatment. No anti-somapacitan antibodies were detected during treatment. Mean insulin-like growth factor-I standard deviation score (IGF-I SDS) at baseline was maintained with both treatments. The majority of the patients had IGF-I SDS values below +2. No significant differences in VAT, SAT and TAT were seen in both treatment groups after 52 weeks (estimated difference, somapacitan – daily GH [95% CI]): –1.74 [–18.13; 14.66], –11.53 [–35.54; 12.48], and –12.85 [–47.31; 21.62] cm2, respectively. TSQM-9 scores were not significantly different between treatments, but showed a tendency in favor of somapacitan (estimated difference [95% CI]): 4.87 [–3.46; 13.20] for effectiveness, 6.79 [–1.04; 14.61] for convenience, and 6.88 [–1.08; 14.85] for overall satisfaction.No new safety concerns were identified. Improvements in body composition were similar in the GH and somapacitan cohorts. The safety and tolerability of somapacitan in Japanese patients with AGHD were consistent with results from the global phase 3 trial (REAL 1).

Biochemical bone turnover markers in hormonal disorders in adults: a narrative review.

Hormonal disorders are often associated with abnormal levels of bone turnover markers (BTMs). N-terminal propeptide of type I procollagen (PINP) and serum C-terminal cross-linking telopeptide of type I collagen (CTX-I) are the reference markers of bone formation and bone resorption, respectively. A comprehensive literature search within the MEDLINE and Web of Science databases was performed. Acromegaly is associated with higher BTM levels, which decrease during the remission after treatment. Adult-onset growth hormone deficiency is often associated with decreased BTM levels. Growth hormone replacement therapy stimulates bone turnover and increases BTM levels. Hypothyroidism is characterized by general slowing of bone metabolism which is reflected by lower BTM levels. The replacement thyroid hormone therapy increases the bone turnover rate and BTM levels increase. Patients with thyroid cancer receive a suppressive dose of thyroid hormones and may have slightly elevated BTM levels. Patients with overt hyperthyroidism had higher BTM levels and anti-thyroid therapy induces a rapid decrease in the BTM levels. Patients with overt primary hyperparathyroidism have higher BTM levels, whereas those with asymptomatic and normocalcemic hyperparathyroidism usually have normal BTM levels. Hypoparathyroidism is characterized by slightly decreased BTM levels. Cushing's syndrome is characterized consistently by markedly decreased osteocalcin concentration, whereas data on other BTMs are discordant. BTMs help us to better understand mechanisms of the impact of hormonal disorders and their treatment on bone metabolism. However, it is unknown whether BTMs may be used to monitor the effect of their treatments on bone in the clinical practice.

Growth hormone therapy in adults with growth hormone deficiency: a critical assessment of the literature.

Growth hormone (GH) therapy has been studied as treatment for clinical manifestations of adult-onset growth hormone deficiency (AO-GHD), including cardiovascular risk, bone health, and quality of life. Patients with AO-GHD typically also have significant history of pituitary pathology and hypopituitarism, which raises the question of what proportion of their clinical presentation can be attributed to GHD alone. Currently, much of the existing data for GH therapy in AO-GHD come from uncontrolled retrospective studies and observational protocols. These considerations require careful reassessment of the role of GH as a therapeutic agent in adult patients with hypopituitarism. We contrast results from placebo-controlled trials with those from uncontrolled and retrospective studies for GH replacement in patients with hypopituitarism. We also examine the evidence for the manifestations of AO-GHD being attributed to GHD alone, as well as the data on adults with congenital, life-long untreated isolated GHD. The evidence for increased morbidity and mortality in hypopituitary patients with GHD, and for the benefits of GH therapy, are conflicting. There remains the possibility that the described clinical manifestations of AO-GHD may not be due to GHD alone, but may also be related to underlying pituitary pathology, treatment history and suboptimal hormone replacement. In the setting of inconsistent data on the benefits of GH therapy, treatment of AO-GHD remains an individualized decision. There is a need for more randomized, placebo-controlled studies to evaluate the long-term outcomes of GH therapy in adults with hypopituitarism.

Change in baseline characteristics over 20 years of adults with growth hormone (GH) deficiency on GH replacement therapy.

Clinical observations over time of adults with growth hormone (GH) deficiency (GHD) have indicated a shift in patient characteristics at diagnosis. The objective of this study was to compare baseline characteristics of patients diagnosed with adult-onset GHD naive to GH replacement during three study periods (1994-1999 (P1), 2000-2004 (P2), and 2005-2012 (P3)) using the KIMS (Pfizer's International Metabolic) database. Data were retrieved for a total of 6069 patients with adult-onset GHD from six countries (Belgium, Germany, Netherlands, Spain, Sweden, and UK): P1 (n = 1705), P2 (n = 2397), and P3 (n = 1967). The proportions of patients with pituitary/hypothalamic tumors and patients with multiple pituitary hormone deficiencies decreased per entry year period, while the proportions with hypertension and diabetes increased. The lag time from diagnosis of pituitary disease to start of GH treatment decreased by 2.9 years over the entry year periods. IGF-1 increased by 0.1 standard deviation score per entry year period. Maximum GH following various stimulation tests, BMI, and waist circumference increased. The use of radiotherapy, glucocorticoid replacement doses, and the proportion of women >50 years on estrogen replacement therapy decreased. The effects of 1 year of GH replacement were similar over the entry year periods despite changes in the patients' baseline characteristics. An expected increase in fasting blood glucose was seen after 1 year of GH treatment. The degree of confirmed GHD became less pronounced and more patients with co-morbidities and diabetes were considered for GH replacement therapy, possibly reflecting increased knowledge and confidence in GH therapy gained with time.

Towards a Göttingen minipig model of adult onset growth hormone deficiency: evaluation of stereotactic electrocoagulation method

BackgroundAdult onset growth hormone (GH) deficiency (AGDH) is a potentially underdiagnosed condition, caused by damage to the pituitary gland. AGHD is treated with growth hormone replacement therapy. A large variety of clinical symptoms and changes in the metabolic homeostasis can be observed and quantified. New large animal models are needed for future drug development. New methodIn this study, we evaluate methods for a new large non-primate animal model of GH deficiency in post pubertal Göttingen Minipigs (minipig). Lesions in the pituitary gland were made by stereotaxic monopolar thermo-coagulation guided by magnetic resonance imaging (MRI), and pituitary function was evaluated using insulin tolerance test (ITT) with measurements of growth hormone secretion induced by hypoglycemia. ResultsLesions were successfully applied to the pituitary gland without any damage to surrounding tissue including the hypothalamus, which was confirmed by post-operative MRI and post mortem histology. Plasma levels of GH during ITT showed no decrease in secreted levels one week after surgery compared to levels obtained before surgery. Comparison with existing methodsCompared to other GH insufficiency models, eloquent brain tissue is spared. Furthermore, alternatively to rodent models, a large animal model would allow the use of human intended equipment to evaluate disease. Using the minipig avoids social, economical and ethical issues, compared with primates. ConclusionThe lesions did not remove all GH production, but proof of concept is demonstrated. In addition, the ITT is presented as a safe and efficient method to diagnose GH deficiency in minipigs.

PMU142 ASSESSING THE HUMAN AND ECONOMIC BURDEN OF SHORT STATURE: A SYSTEMATIC LITERATURE REVIEW

We sought to better understand the human and economic burden of short stature (SS) using a systematic literature review. Studies of the human and economic burden of SS in adults and children, due to any cause, were searched using Embase, MEDLINE and Cochrane databases in December 2018, capturing publications from 2008 onwards. Case series and populations with adult-onset growth hormone deficiency (GHD) were excluded. Of 1239 publications identified, 26 studies (17 in children, 9 in adults) met inclusion criteria, with sample sizes of the SS populations ranging from 15 to 285. Thirteen studies were in mixed populations, four in GHD only, four in chronic kidney disease (CKD), and one each in Turner syndrome, Prader-Willi syndrome, skeletal dysplasia, congenital adrenal hyperplasia, and childhood-onset multiple pituitary hormone deficiency. No economic studies were identified. Twelve studies compared quality of life (QoL) in children with SS and those with normal height; 10 found that QoL was significantly poorer in children with SS and two (both in CKD populations) found no association. Of five studies that investigated height as a predictor of QoL among children with SS, all found greater height was associated with better QoL. One study highlighted negative social experiences in children with SS. Two studies evaluated cognitive function, finding cognitive scores were significantly poorer in children with SS than in those with normal height. In adults, six studies demonstrated impaired QoL with SS versus normal height, while two found no association and one reported mixed results. The literature suggests that compared with those with normal height, children and adults with SS of any cause experience poorer QoL and in children it may negatively impact social and cognitive functioning. Further research could extend our understanding of the human and economic burden in this field.