Insulin-like Growth factor-I SDS Research Articles

THU174 Model-Based Analysis Of IGF-I Response, Dosing, And Monitoring For Once-Weekly Somapacitan In Children With GH Deficiency

Abstract Disclosure: R.J. Kildemoes: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. Y. Kamal Lyauk: Employee; Self; Novo Nordisk. J.C. Blair: Speaker; Self; Novo Nordisk, Pfizer, Inc., Ipsen. Other; Self; Novo Nordisk. B.S. Miller: Consulting Fee; Self; Novo Nordisk, Abbvie, Endo Pharmaceuticals, Ascendis Pharma, Bristol-Myers Squibb, Pfizer, Inc., EMD Serono, BioMarin Pharmaceutical, Tolmar. Research Investigator; Self; Alexion Pharmaceuticals, Inc., Abbvie, Aeterna Zentaris, Amicus, Lumos Pharma, Novo Nordisk, Lysogene, OPKO Health, Pfizer, Inc., Prevail Therapeutics, Sangamo Therapeutics. J. Mori: None. M. Højby Rasmussen: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. P.F. Backeljauw: Consulting Fee; Self; Novo Nordisk, Novartis Pharmaceuticals, Ascendis Pharma, BioMarin Pharmaceutical, Tolmar Pharmaceuticals, Cavalry Biosciences, Ipsen. Research Investigator; Self; Novo Nordisk, Novartis Pharmaceuticals, Ipsen. Growth hormone (GH) replacement therapy improves overall health and adult height in children with GH deficiency (GHD). GH stimulates insulin-like growth factor-I (IGF-I) release, the biomarker commonly used for guiding GH dose adjustments to ensure optimal long-term safety and efficacy. This study aims to provide model-based insights into the dose-IGF-I responses of once-weekly somapacitan, a novel long-acting GH, compared to daily GH in pediatric patients with GHD. Pharmacokinetic/pharmacodynamic (PK/PD) modeling was used to characterize somapacitan dose-IGF-I response and to predict the response to change of dosing day and missed dosing of somapacitan. Analyses included dosing information and 1473 PK samples from 210 GHD patients treated with somapacitan across three trials: phase 1 (NCT01973244), phase 2 (NCT02616562; REAL3), and phase 3 (NCT03811535; REAL4), as well as 1381 IGF-I samples from 186 GHD patients treated with somapacitan from REAL3 and REAL4. A clear dose-response relationship was observed with increasing somapacitan exposure and increasing change from baseline IGF-I SDS. A linear model permitted the development of a tool to calculate the estimated average weekly IGF-I exposure from a single IGF-I sample obtained at any time within the somapacitan dosing interval at steady state. In practice, the use of this tool will require knowledge of the timing of the somapacitan injection relative to the timing of the IGF-I sample collection. IGF-I SDS simulations support flexible dosing day changes while maintaining a minimum of 4 days between doses. In this study, we present a practical guide that may inform clinicians about the expected weekly average IGF-I concentration in somapacitan-treated pediatric patients with GHD from a single sample taken on any chosen day during the weekly dosing interval. The ability to determine weekly average IGF-I enhances our understanding of somapacitan dosing and should support physicians in monitoring long-term safety and efficacy of this therapy. Furthermore, we provide insights on flexibility to change of dosing day and missed dosing of somapacitan. Presentation: Thursday, June 15, 2023

Factors affecting IGF-I level and correlation with growth response during growth hormone treatment in LG Growth Study.

Growth hormone treatment strategies to achieve the goal include the titration of GH doses according to serum insulin-like growth factor I (IGF-I) concentrations. However, IGF-I levels do not always correlate well with the growth response. This study aims to identify the factors affecting the IGF-I concentration and identify the relationship between IGF-I and the treatment response. The data of prepubertal children treated with recombinant human GH for more than one year were obtained from the LG Growth Study (LGS) Database. This study includes patients with idiopathic growth hormone deficiency (IGHD), organic growth hormone deficiency (OGHD), or Turner syndrome (TS) or small for gestational age (SGA). Among 2,021 participants registered in LGS, 366 subjects were selected, 252 had IGHD, 16 had OGHD, 31 had TS, and 67 were SGA. In the IGHD and SGA groups, IGF-I levels had a positive correlation with weight SDS. There was no significant relationship between the pre-treatment IGF-I level and growth response. However, in the IGHD group, the growth response was significantly higher when the change in the IGF-I SDS value was 1 or more (p = 0.0013). Therefore, IGF-I concentrations should be used as an indicator to monitor the treatment compliance rather than for efficacy determination in Korean children of short stature with GH treatment.

Patients with low IGF-I after curative surgery for Cushing's syndrome have an adverse long-term outcome of hypercortisolism-induced myopathy.

Glucocorticoid excess leads to muscle atrophy and weakness in patients with endogenous Cushing's syndrome. Insulin-like growth factor I (IGF-I) is known to have protective effects on muscle loss. We hypothesized that individual serum IGF-I concentrations might be predictive for long-term myopathy outcome in Cushing's syndrome. In a prospective longitudinal study of 31 patients with florid Cushing's syndrome, we analyzed IGF-I and IGF binding protein 3 (IGFBP 3) concentrations at the time of diagnosis and following surgical remission over a period of up to 3 years. We assessed muscle strength by grip strength measurements using a hand grip dynamometer and muscle mass by bio-impedance measurements. Individual serum IGF-I concentrations in the postoperative phase were strongly predictive of long-term grip strength outcome (rs = 0.696, P ≤ 0.001). Also, lower IGF-I concentrations were associated with a lower muscle mass after 3 years (rs = 0.404, P = 0.033). While patients with high IGF-I s.d. scores (SDS; >1.4) showed an improvement in grip strength within the follow-up period (P = 0.009), patients with lower IGF-I SDS (≤-0.4) had a worse outcome with persisting muscle dysfunction. In contrast, preoperative IGF-I concentrations during the florid phase of Cushing's syndrome did not predict long-term muscle function outcome (rs = 0.285, P = 0.127). Lower individual IGF-I concentrations 6 months after curative surgery for Cushing's syndrome are associated with adverse long-term myopathy outcome and IGF-I might be essential for muscle regeneration in the early phase after correction of hypercortisolism.

Phenotypic and genotypic features of a large kindred with a germline AIP variant.

Acromegaly is usually a sporadic disease, but familial cases occur. Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are associated with familial pituitary adenoma predisposition. However, the pathogenicity of some AIP variants remains unclear and additional unknown genes may be involved. To explore the phenotype and genotype of a large kindred carrying the p.R304Q AIP variant. The family comprised 52 family members at risk of carrying the p.R304Q AIP variant including a case with gigantism and one with acromegaly and several family members with acromegalic features. Nine family members (three trios) underwent exome sequencing to identify putative pathogenic variants. We identified 31 p.R304Q carriers, and based on two cases with somatotropinomas, the disease penetrance was 6%. We observed physical signs of acromegaly in several family members, which were independent of AIP status. Serum insulin-like growth factor-I (IGF-I) levels in all family members were above the mean for age and sex (IGF-I SDS: +0.6 [CI95% +0.4-0.9], P<.01). Exome analysis identified two candidate genes: PDE11A, known to be associated with the development of adrenal tumours, and ALG14. Ten asymptomatic p.R304Q family members (age >50years) were screened for the PDE11A and ALG14 variant; both variants were present in five of ten persons. This large family adds new information on the p.R304Q AIP variant, and data suggest two new candidate genes could be associated with growth hormone excess.

SAT-090 Factors Affecting IGF-1 Level and Correlation with Growth Response During Growth Hormone Treatment in LGS Patients

Background: Primary goal of growth hormone (GH) treatment for short children is to achieve an adult height in the normal range. Different GH treatment strategies to achieve this goal include titration of GH dose according to serum insulin-like growth factor I (IGF-I) concentrations. However, IGF-I levels do not always correlate well with the growth response. The purpose of this study is to identify the factors affecting IGF-I concentration in each disease and to correct the related factors and then to identify the relationship between IGF-1 and treatment response. Methods: In this study, data of pre-pubertal children with idiopathic growth hormone deficiency (IGHD), organic GHD (OGHD), Turner syndrome (TS), small for gestational age (SGA) who were treated with recombinant human GH more than one year were obtained from the LGS Database. The LGS has been progressing since 2012 and is an open-label, multicenter, prospective, and retrospective observational study. Results: Among 2,021 registered in LGS, the subjects were 366 except for the violation of selection criteria. Among them, IGHD was 252, 16 OGHD, 31 TS, and 67 SGA. The mean age of IGHD was 6.02, and the mean bone age was 4.49 years. OGHD was 7.38, 5.74, TS was 7.13, 6.52, and SGA was 5.61, 4.96 years. The height SDS according to chronologic age was -2.76 in IGHD group, OGHD -2.33, TS -2.9, SGA -2.57. In the IGHD and SGA group, IGF-I level has a positive correlation with weight and BMI (weight; r=0.0071 in IGHD, r=0.0009 in SGA, BMI; r=0.0411 in IGHD, r=0.003 in SGA). IGF-I showed a negative correlation with chronological age in the IGHD group (r=0.0411) and mid-parental height in the SGA group (r=0.0069). There was no significant relationship between pretreatment IGF-I level and growth response. However, in the IGHD group, the growth response was significantly higher when the change in IGF-I SDS value was 1 or more (P=0.0013). Conclusion: This study is the first study using LGS data to identify factors affecting IGF-I levels in Korean children with short stature and the relationship with treatment response. IGF-I levels were positively correlated with body weight in IGHD and SGA groups. There was no significant relationship between pre-treatment IGF-I levels and post-treatment growth response. In conclusion, IGF-I concentrations should be used as a tool for treatment compliance rather than for efficacy determination.

Frequency of oligosymptomatic gastrointestinal tract diseases and its relation to insulin-like growth factor I in idiopathic (non-GH-deficient) short stature children.

IntroductionThere is a discussion about growth hormone therapy in idiopathic short stature (ISS) children. To diagnose ISS, it is necessary to exclude other diseases; gastrointestinal tract diseases (GIDs) are among them. However, GID symptoms may be scarce. The aim of the study was to evaluate the frequency of unexpected oligosymptomatic GIDs in ISS and assess their influence on auxological parameters and insulin-like growth factor I (IGF-I) concentration.Material and methodsThe analysis included 101 children with ISS and 95 controls. All patients were tested for celiac disease (CD), inflammatory bowel disease (IBD), lactose malabsorption (LM), cystic fibrosis (CF), Helicobacter pylori (HP) and Ascaris sp. (Asc) infections, as well as Candida albicans (Calb) colonization, by applying simple blood and stool tests and gastrofiberoscopy.ResultsIn 75.2% of short children, one or more than one GIDs listed above were diagnosed, with the highest frequency of: Calb (46.5%), LM (33.7%), HP (24.7%) and/or Asc (21.8%). The incidence of GIDs was significantly higher than in the control group. The GID frequency increases with the age of children. In most ISS children, the IGF-I SDS was below –1.0 and it was the lowest in children with HP (p < 0.05).ConclusionsHigh frequency of unexpected oligosymptomatic GIDs in children diagnosed with ISS indicates the need to search for gastrointestinal (GI) causes in each case of short stature in children. The pathomechanisms responsible for short stature in these cases may vary, although it seems that reduced production of IGF-I plays an important role.

Efficacy and safety of two doses of Norditropin® (somatropin) in short stature due to Noonan syndrome: a 2-year randomized, double-blind, multicenter trial in Japanese patients.

This randomized double-blind multicenter trial (NCT01927861) evaluated the growth-promoting effect and safety of Norditropin® (NN220; somatropin) in Japanese children with short stature due to Noonan syndrome. Prepubertal children aged 3-<11 years (boys) or 3-<10 years (girls) with Noonan syndrome were randomized to receive GH 0.033 mg/kg/day (n = 25, mean age 6.57 years, 11 females) or 0.066 mg/kg/day (n = 26, mean age 6.06 years, eight females) for 104 weeks. Change in height standard deviation score (HSDS) from baseline was analyzed based on an ANCOVA model. Baseline HSDS was -3.24. Estimated change in HSDS [95% CI] after 104 weeks' treatment was 0.84 [0.66, 1.02] and 1.47 [1.29, 1.64] for the lower and higher doses, respectively; estimated mean difference 0.63 [0.38, 0.88], p < 0.0001. Rates and patterns of adverse events (AEs) were similar between groups. Most were mild and reported as unlikely to be related to Norditropin®. There were no withdrawals due to AEs. Insulin-like growth factor-I SDS increased from -1.71 to -0.64 (0.033 mg/kg/day) and to 0.63 (0.066 mg/kg/day). HbA1c increased slightly (0.033 mg/kg/day: +0.14%; 0.066 mg/kg/day: +0.13%); glucose profiles were almost unchanged; insulin profiles increased in both groups in the oral glucose tolerance test. There were no clinically significant abnormal electrocardiogram or echocardiography findings. We conclude that Norditropin® at doses of 0.033 mg/kg/day or 0.066 mg/kg/day for 104 weeks increases height in Japanese children with short stature due to Noonan syndrome, with a favorable safety profile. The effect was greater with 0.066 mg/kg/day compared with 0.033 mg/kg/day.

Long-Term Growth Hormone Therapy is Associated With a Dose-Dependent Increase in Height SDS and Insulin-Like Growth Factor-I SDS in Short Japanese Children Born Small for Gestational Age

In children with short stature born small for gestational age (SGA), growth hormone (GH) treatment is associated with an acceleration of growth allowing most to achieve an adult height adequate for their target height. The pathophysiology of growth failure may arise from anomalies in the GH–IGF axis, including deficits in GH/IGF-I concentrations and/or GH/IGF-I sensitivity.

Cardiovascular changes in patients with adult-onset growth hormone deficiency assessed by CMR

Summary The study investigated cardiovascular changes in adultonset growth hormone deficiency (GHD) and showed that patients with adult-onset GHD have a left ventricular mass index (LVMi) at or below the lower limit of normal, which improves with one year of growth hormone replacement. Background GHD causes cardiovascular problems, with loss of cardiac response to exercise and increased cardiac mortality, however the underlying processes are poorly understood. Methods Ten patients with adult-onset GHD and age- and sexmatched controls (n=10) underwent CMR. Patients underwent scans before disease treatment and at twelve months after treatment. Cardiac parameters were calculated and indexed to body surface area (BSA). The comparison between groups was done using Mann-UWhitney test and within the group using Wilcoxon test. The data are presented as median values. Results Patients with GHD did not have significantly different left ventricle (LV) mass or volumetric parameters from controls: LV mass index (LVMi) 55.0 vs. 56.6 g/m 2 , p=0.315; end diastolic volume index (EDVi) 69.2 vs. 76.3 ml/m 2 , p=0.1655; end systolic volume index (ESVi) 24.8 vs. 28.3 ml/m 2 , p=0.3527 and ejection fraction (EF) 64 vs. 63 %, p=0.8197. However, patients had an LVMi beneath the lower limit of normal when compared to published normal ranges (55.4 - 74.0 g/m 2 ). There were no differences between right ventricular (RV) EDVi (68.0 vs. 80.8 ml/m 2 , p=0.393), ESVi (26.2 vs. 27.5, p=0.7394) and EF (63 vs. 61 %, p=0.9696) in the GHD group and controls. Patients with GHD on GH treatment for 1 year showed an increase in median insulin-like growth factor I (IGF-I) SDS from -1.83 to +0.40 (p=0.0068). There was no correlation between LVMi and IGF-I SDS (r=0.164, p=0.657). At one year the median LVMi moved into the previously published normal range (55.0 to 63.0 g/m 2 , normal range 55.4 - 74.0) achieving statistical significance compared to pre-treatment values (p=0.0156). Conclusions Patients with adult-onset GHD have an LVMi at or below the lower limit of normal, which improves with one year of growth hormone replacement.

Identification of factors associated with good response to growth hormone therapy in children with short stature: results from the ANSWER Program®.

ObjectiveTo identify factors associated with growth in children on growth hormone (GH) therapy using data from the American Norditropin Studies: Web-enabled Research (ANSWER) Program® registry.MethodsGH-naïve children with GH deficiency, multiple pituitary hormone deficiency, idiopathic short stature, Turner syndrome, or a history of small for gestational age were eligible (N = 1,002). Using a longitudinal statistical approach, predictive factors were identified in patients with GHD for change from baseline in height standard deviation score (ΔHSDS) following 2 years of treatment.ResultsGradual increases in ΔHSDS over time were observed for all diagnostic categories. Significant predictive factors of ΔHSDS, ranked by significance were: height velocity (HV) at 4 months > baseline age > baseline HSDS > baseline body mass index (BMI) SDS > baseline insulin-like growth factor I (IGF-I) SDS; gender was not significant. HV at 4 months and baseline BMI SDS were positively correlated, whereas baseline age, HSDS, and IGF-I SDS were negatively correlated with ΔHSDS.ConclusionsThese results may help guide GH therapy based on pretreatment characteristics and early growth response.

The benefit of long-term growth hormone (GH) replacement therapy in hypopituitary adults with GH deficiency: Results of the German KIMS database

Objective To evaluate the treatment effects of long-term growth hormone (GH) replacement therapy in adults with GH deficiency (GHD) who were followed in KIMS Germany (Pfizer International Metabolic Database), a national surveillance study. Design The analysis was performed using baseline and long-term data (range: 4–10 years) of 440 consecutively documented patients (216 women and 224 men) with GHD, aged 20 to 49 years, enrolled in KIMS Germany. Serum insulin-like growth factor I (IGF-I), fasting blood glucose, fasting serum total cholesterol and low-density lipoprotein cholesterol (LDL-C) as well as body mass index (BMI), waist circumference (WC) and hip circumference (HC) at baseline and at last visit were studied. Furthermore, QoL-AGHDA score was determined to assess quality-of-life (QoL). Results The mean dose of GH over all years was 0.41 mg per day in women and 0.37 mg per day in men. IGF-I and IGF-I SDS levels (standard deviation score) increased significantly (p < 0.001) during GH treatment. The QoL-AGHDA score decreased significantly (p < 0.001), indicating long-lasting improvement in QoL. In total cholesterol, LDL-C and fasting blood glucose, no significant changes were found. Only six patients developed type 2 diabetes during follow-up. Females and males similarly increased significantly in BMI, WC and HC. During GH treatment, recurrences of pituitary or central nervous system tumours or further de novo neoplasia were reported in 6 or 11 patients, respectively. The number of the most frequently reported GH treatment-associated adverse events was low. Conclusion These observational data show long-term beneficial effects of GH replacement therapy on QoL and show no significant effects on total cholesterol, LDL-C or BMI, WC and HC. Additionally, our data indicate that GH replacement therapy in adults is well tolerated.

Ten-year GH replacement increases bone mineral density in hypopituitary patients with adult onset GH deficiency

There are few studies that have determined the effects of long-term GH replacement on bone mineral density (BMD) in GH-deficient (GHD) adults. In this study, the effects of 10 years of GH replacement on BMD were assessed in 87 GHD adults using dual energy X-ray absorptiometry (DEXA). The results show that GH replacement induced a sustained increase in BMD at all the skeletal sites measured. Little is known of the effect of more than 5 years of GH replacement therapy on bone metabolism in GHD adults. In this prospective, open-label, single-center study, which included 87 consecutive adults (52 men and 35 women; mean age of 44.1 (range 22-74) years) with adulthood onset GHD, the effect of 10 years of GH replacement on BMD was determined. The mean initial dose of GH was 0.98 mg/day. The dose was gradually lowered and after 10 years the mean dose was 0.47 mg/day. The mean insulin-like growth factor-I (IGF-I) SDS increased from 1.81 at baseline to 1.29 at study end. The GH replacement induced a sustained increase in total, lumbar (L2-L4) and femur neck BMD, and bone mineral content (BMC) as measured by DEXA. The treatment response in IGF-I SDS was more marked in men, whereas women had a more marked increase in the total body BMC and the total body z-score. There was a tendency for women on estrogen treatment to have a larger increase in bone mass and density compared with women without estrogen replacement. Ten years of GH replacement in hypopituitary adults induced a sustained, and in some variables even a progressive, increase in bone mass and bone density. The study results also suggest that adequate estrogen replacement is needed in order to have an optimal response in BMD in GHD women.

Serum leptin and IGF-I during growth hormone treatment in chronic renal failure.

Serum leptin decreases during growth hormone (hGH) treatment and pre-treatment values have been suggested as a predictor of the response to hGH in GH deficiency (GHD) but not in non-GHD syndromes. To investigate whether this holds true in children with chronic renal failure (CRF), we evaluated changes in serum leptin, insulin-like growth factor-I (IGF-I) and height before(b) and during the 1st year (3 months, 6 months, 9 months, 12 months) of hGH treatment (1 IU/kg per week) in 11 children (median age(b) 10.1 years, mean height(b) -2.9 SDS) with CRF. Serum leptin and IGF-I were compared with values from healthy children. Each patient also served as his/her own control, with values during treatment compared with those before treatment. Growth improved in all patients during treatment (mean change(12 m) +7.2 cm, change in height SDS(12 m) +0.5, P=0.001). Weight decreased (median decrease(12 m) 0.3 SDS, P=0.02) but body mass index (BMI) and serum leptin did not change during treatment. Serum IGF-I levels were low before (mean -1.1 SDS) but increased during hGH treatment, the increment being greatest at 10 days (mean increment +1.9 SDS, P<0.0001). Serum leptin(b) did not correlate with change in serum IGF-I(10d), height(12 m) or weight(12 m). Serum IGF-I SDS(b) correlated with height SDS at 12 months ( r=0.80, P=0.006) of hGH treatment. Serum leptin(b) correlated with BMI ( r(s)=0.75, P=0.01). Levels adjusted for BMI did not differ from values in healthy children and did not change during treatment. Despite an IGF-I and growth response during hGH treatment, serum leptin did not change and pre-treatment values did not predict the growth response in these children with CRF.

Short stature in Duchenne muscular dystrophy: a study of 34 patients

In Duchenne muscular dystrophy (DMD), short stature is a feature of unknown cause. This cross-sectional study of 34 male patients (mean age 8.0 y, age range 1.2-13.7 y) was conducted to examine the relationship between auxological parameters, markers of growth and the extent of muscular weakness. Weight and length at birth (SDS +/- SD; 0.0 +/- 1.2; 0.2 +/- 1.5) and target height SDS (-0.2 +/- 0.7) were normal. Height (HT) SDS (-1.0 +/- 1.1) was lower than the normal population (p < 0.001) and did not correlate with age. Body mass index SDS (-0.1 +/- 1.6) was normal. Tests of insulin-like growth factor-I SDS (-0.6 +/- 1.2) and insulin-like growth factor binding protein-3 SDS (0.1 +/- 1.3) ruled out a severe derangement in the GH-IGF-axis. The carboxy-terminal propeptide of type I procollagen (PICP) SDS (0.6 +/- 1.5) was normal, but bone-specific alkaline phosphatase (BAP) SDS (-1.7 +/- 0.8) was low (p <0.001). HT SDS did not correlate with BAP SDS. The Vignos scale, a grading of muscular function (score: 0 = unaffected; 11 = confined to bed) (median (range): 3 (0-9)) correlated strongly with age (r = 0.77, p < 0.0001), but did not correlate with HT SDS, PICP SDS or BAP SDS. In conclusion, DMD patients are significantly shorter than the normal population, though the HT SDS does not change with age. Growth hormone deficiency does not seem to be the cause of short stature in DMD. Significantly low BAP levels are probably the result of the reduced muscle mass, which leads to a lower biomechanical load on the bone and thus a reduction in bone turnover. The short stature observed in our study is unlikely to be the result of muscular weakness.

Effect of growth hormone treatment in patients with chronic fatigue syndrome: A preliminary study

The efficacy of growth hormone (GH) therapy was evaluated in patients with chronic fatigue syndrome (CFS) who had peak serum GH levels below 10 microg/l during stage-controlled sleep. Twenty patients (7 men, 13 women; age range, 30-60 years) with CFS were randomized to receive placebo or GH therapy, 6.7 microg/kg/day (0.02 IU/kg/day), for 12 weeks. Following this double-blind treatment period, the 17 patients remaining in the study were given GH therapy at the above dose for an open period of 9 months. Mean (+/- SD) serum levels of insulin-like growth factor I (IGF-I) increased during GH treatment, from 173 +/- 46 microg/I to 296 +/- 89 microg/l (P < 0.001); IGF-I SDS values increased from -0.45 +/- 1.14 to +1.43 +/- 1.09 (P < 0.001). Fat-free mass and total body water were significantly increased after 12 months of treatment. Although quality of life, as assessed using two different questionnaires, did not improve significantly during GH treatment, four patients were able to resume work after a long period of sick leave.

Secretion of growth hormone in patients with chronic fatigue syndrome

Decreased serum levels of insulin-like growth factor I (IGF-I) are common in patients with fibromyalgia, which is frequently associated with chronic fatigue syndrome (CFS). Twenty patients with CFS (7 men, 13 women; age range, 30-60 years) and age- and sex-matched controls were tested for peak GH responses to insulin-induced hypoglycaemia and arginine administration. Nocturnal secretion of GH and serum levels of IGF-I were also measured. Serum IGF-I SDS (+/- SD) was significantly lower in patients with CFS than in controls (SDS, -0.39 +/- 1.07 vs 0.33 +/- 0.84; P = 0.02). Patients with CFS also tended to have reduced nocturnal secretion of GH (area under the curve, 32.4 +/- 18.3 vs 62.7 +/- 43.7 microg/l/15 minutes; P= 0.06), but peak GH responses to insulin-induced hypoglycaemia and arginine administration did not differ significantly between the two groups. It is not clear whether the tendency for impaired spontaneous nocturnal GH secretion in patients with CFS is a cause or an effect of the condition.