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The Journal of Clinical Endocrinology... Sep 2023Despite having normal growth hormone (GH) secretion, individuals with Turner syndrome (TS) have short stature. Treatment with recombinant human GH is recommended for TS...
CONTEXT
Despite having normal growth hormone (GH) secretion, individuals with Turner syndrome (TS) have short stature. Treatment with recombinant human GH is recommended for TS girls with short stature.
OBJECTIVE
This work aimed to evaluate the effectiveness and safety of Norditropin (somatropin, Novo Nordisk) with up to 10 years of follow-up in children with TS.
METHODS
Secondary analysis was conducted of Norditropin data from 2 non-interventional studies: NordiNet® IOS (NCT00960128) and the ANSWER program (NCT01009905).
RESULTS
A total of 2377 girls with TS were included in the safety analysis set (SAS), with 1513 in the treatment-naive effectiveness analysis set (EAS). At the start of treatment, 1273 (84%) participants were prepubertal (EAS); mean (SD) age was 8.8 (3.9) years. Mean (SD) dose received at the start of GH treatment was 0.045 (0.011) mg/kg/day (EAS). Mean (SD) baseline insulin-like growth factor-1 (IGF-I) SD score (SDS) was -0.86 (1.52), and mean (SD) duration of GH treatment (SAS) was 3.8 (2.8) years.Height SDS (HSDS) increased throughout follow-up, with near-adult HSDS reached by 264 (17%) participants (mean [SD] -1.99 [0.94]; change from baseline +0.90 [0.85]). During the study, 695 (46%) participants (EAS) entered puberty at a mean (SD) age of 12.7 (1.9) years (whether puberty was spontaneous or induced was unknown). Within the SAS, mean IGF-I SDS (SD) at year 10 was 0.91 (1.69); change from baseline +1.48 (1.70). Serious adverse reactions were reported in 10 participants (epiphysiolysis [n = 3]).
CONCLUSION
GH-treated participants with TS responded well, without new safety concerns. Our real-world data are in agreement with previous studies.
Topics: Adult; Child; Female; Humans; Body Height; Dwarfism, Pituitary; Growth Disorders; Human Growth Hormone; Insulin-Like Growth Factor I; Turner Syndrome; Child, Preschool
PubMed: 36947589
DOI: 10.1210/clinem/dgad159 -
Best Practice & Research. Clinical... Dec 2023
Topics: Adult; Humans; Endocrinology; Dwarfism, Pituitary; Hypopituitarism; Growth Hormone; Human Growth Hormone
PubMed: 37993350
DOI: 10.1016/j.beem.2023.101840 -
The Journal of Clinical Endocrinology... Aug 2023Patients with adult growth hormone deficiency (AGHD) are at increased risk of metabolic syndrome. Metabolic profiles in AGHD patients have been insufficiently evaluated.
CONTEXT
Patients with adult growth hormone deficiency (AGHD) are at increased risk of metabolic syndrome. Metabolic profiles in AGHD patients have been insufficiently evaluated.
OBJECTIVE
This work aims to explore serum metabolite profiles by metabolomics analysis and assess potential metabolites associated with recombinant human growth hormone (rhGH) treatment.
METHODS
Thirty-one AGHD patients and 31 healthy controls were enrolled. Untargeted ultra-performance liquid chromatography-coupled mass spectroscopy was conducted in all patients and controls at baseline and during 12 months of rhGH treatment in 11 AGHD patients. Data were processed by principal component analysis, variable importance in projection scoring, orthogonal partial least squares-discriminant analysis, and MetaboAnalyst 5.0. We further explored the associations between metabolites and clinical parameters.
RESULTS
Metabolomics indicated a distinct metabolic pattern between AGHD patients and healthy controls. The perturbed pathways mainly include the biosynthesis of unsaturated fatty acids, sphingolipid metabolism, glycerophospholipid metabolism, fatty acid elongation, degradation, and biosynthesis. rhGH treatment increased the levels of specific glycerophospholipids compounds and reduced fatty acid ester compounds. Significant correlations existed between the 40 identified metabolites and insulin-like growth factor-1 SD score (IGF-1 SDS), body composition, and glucose and lipid metabolism plasma markers. During rhGH treatment, there was a statistically significant negative correlation between deoxycholic acid glycine conjugate and waist-to-hip ratio, while a statistically significant positive correlation existed between decanoylcarnitine and serum low-density lipoprotein levels.
CONCLUSION
AGHD patients have unique metabolomic profiles. rhGH treatment alters the serum levels of several fatty acid compounds/amino acids, which may contribute to the improvement of metabolic status in AGHD patients.
Topics: Humans; Adult; Chromatography, High Pressure Liquid; Human Growth Hormone; Dwarfism, Pituitary; Metabolomics; Fatty Acids; Mass Spectrometry
PubMed: 36883594
DOI: 10.1210/clinem/dgad129 -
Indian Pediatrics Feb 2024To analyse the clinical and radiological characteristics of pituitary stalk interruption syndrome (PSIS).
OBJECTIVE
To analyse the clinical and radiological characteristics of pituitary stalk interruption syndrome (PSIS).
METHODS
A retrospective analysis of confirmed cases of PSIS was performed. The development of new pituitary hormonal deficiencies and response to recombinant human growth hormone (rhGH) therapy were assessed during follow-up.
RESULTS
This study included 14 children (10 boys) of PSIS with median (range) age of 12.15 years (2 months - 18 years). Short stature was the most common presentation (n = 13), and micropenis (n = 4), cleft lip (n = 1) and single central incisor (n = 1) were other midline defects. Growth hormone (GH) deficiency was present in 14 children and 7 of them also had multiple pituitary hormone deficiencies at baseline. Central hypothyroidism (n = 5), secondary adrenal deficiency (n = 4) and gonadotropin deficiencies (n = 2) were also seen. All children received rhGH. The mean height gain on follow-up was 12.78 cm in first year (n = 14), 6.5 cm in second year (n = 8) and 4.07 cm in third year (n = 7) of rhGH therapy. Four children developed additional pituitary hormone deficiency on follow-up.
CONCLUSION
Short stature with isolated GH deficiency was the most common presentation of PSIS that showed good response to rhGH therapy.
Topics: Child; Humans; Male; Dwarfism, Pituitary; Growth Hormone; Human Growth Hormone; Hypopituitarism; Pituitary Gland; Retrospective Studies; Female; Infant; Child, Preschool; Adolescent
PubMed: 38321728
DOI: No ID Found -
Archives de Pediatrie : Organe Officiel... Nov 2023We aimed to evaluate the relation between the peak growth hormone (GH) levels in provocation tests and response to recombinant human GH (rhGH) therapy in patients with...
BACKGROUND
We aimed to evaluate the relation between the peak growth hormone (GH) levels in provocation tests and response to recombinant human GH (rhGH) therapy in patients with GH deficiency (GHD).
METHODS
This was a cross-sectional, single-center, and retrospective study. A total of 135 patients under the age of 16 years who were diagnosed with GHD through insulin tolerance tests and L-DOPA stimulation tests and who received rhGH therapy for at least 2 years in the Pediatric Endocrinology Clinic of Akdeniz University Hospital between 1997 and 2021 were included in the study.
RESULTS
The patients were divided into two groups: idiopathic GHD (group I, n = 119) and multiple pituitary hormone deficiencies or organic pathology on magnetic resonance imaging (group II, n = 16). The patients in group I were classified into three subgroups according to the peak GH values in the provocation tests (group Ia: peak GH <3 μg/L, n = 34; group Ib: peak GH between 3 and 7 μg/L, n = 71; group Ic: peak GH between 7 and 10 μg/L, n = 34). The median age was 11.5 years in group I (8.8 in group Ia, 12.1 in group Ib, 12.3 in group Ib) and 8.8 years in group II. The height standard deviation score (SDS) was -2.93 in group I (-2.85 in group Ia, -2.99 in group Ib, -2.94 in group Ic) and -3.79 in group II. The median Δheight SDS was 0.61 in group I and 1.05 in group II at the end of the first year of treatment and 0.31 in group I and 0.45 in group II at the end of the second year (p = 0.005 and p = 0.074, respectively). When the subgroups of group I were compared, height SDS, Δheight SDS, and height velocity (HV) SDS were all higher in group Ia at the end of the first year of rhGH therapy (p = 0.040, p = 0.029, and p = 0.005, respectively). The height SDS was still significantly higher in group Ia (p = 0.033) while the HV SDS and Δheight SDS were similar between the groups at the end of the second year of therapy (p = 0.164 and p = 0.522, respectively). There was a statistically significant association between the first-year HV SDS and the peak GH value in provocation tests in multiple regression analyses (p<0.001). In addition, the final model revealed that height SDS and weight SDS at the start of the treatment and the first-year HV SDS are the factors with a statistically significant effect on the second-year HV SDS (p = 0.022, p = 0.001, and p<0.001, respectively).
CONCLUSION
Our findings show that the lower the GH peak in provocation tests, the better the response to treatment. The best HV was observed in the first year of rhGH therapy, and the diagnosis should be checked in those patients who had a low first-year HV and did not have a severely low GH peak in provocation tests.
Topics: Humans; Child; Adolescent; Retrospective Studies; Cross-Sectional Studies; Body Height; Human Growth Hormone; Dwarfism, Pituitary; Growth Hormone
PubMed: 37802668
DOI: 10.1016/j.arcped.2023.08.005 -
Growth Hormone & IGF Research :... Aug 2023Traumatic brain injury (TBI), a common cause of adult growth hormone deficiency (AGHD), affects 20% of Veterans returning from Iraq and Afghanistan (OEF/OIF/OND). Growth... (Observational Study)
Observational Study
OBJECTIVE
Traumatic brain injury (TBI), a common cause of adult growth hormone deficiency (AGHD), affects 20% of Veterans returning from Iraq and Afghanistan (OEF/OIF/OND). Growth hormone replacement therapy (GHRT) improves quality of life (QoL) in AGHD but remains unexplored in this population. This pilot, observational study investigates the feasibility and efficacy of GHRT in AGHD following TBI.
DESIGN
In this 6-month study of combat Veterans with AGHD and TBI starting GHRT (N = 7), feasibility (completion rate and rhGH adherence) and efficacy (improvements in self-reported QoL) of GHRT were measured (primary outcomes). Secondary outcomes included body composition, physical and cognitive function, psychological and somatic symptoms, physical activity, IGF-1 levels and safety parameters. It was hypothesized that participants would adhere to GHRT and that QoL would significantly improve after six months.
RESULTS
Five subjects (71%) completed all study visits. All patients administered daily rhGH injections, 6 (86%) of whom consistently administered the clinically-prescribed dose. While QoL demonstrated numeric improvement, this change did not reach statistical significance (p = 0.17). Significant improvements were observed in total lean mass (p = 0.02), latissimus dorsi strength (p = 0.05), verbal learning (Trial 1, p = 0.02; Trial 5, p = 0.03), attention (p = 0.02), short-term memory (p = 0.04), and post-traumatic stress disorder (PTSD) symptoms (p = 0.03). Body weight (p = 0.02) and total fat mass (p = 0.03) increased significantly.
CONCLUSION
GHRT is a feasible and well-tolerated intervention for U.S. Veterans with TBI-related AGHD. It improved key areas impacted by AGHD and symptoms of PTSD. Larger, placebo-controlled studies testing the efficacy and safety of this intervention in this population are warranted.
Topics: Adult; Humans; Growth Hormone; Quality of Life; Pilot Projects; Human Growth Hormone; Dwarfism, Pituitary; Brain Injuries, Traumatic; Hormone Replacement Therapy
PubMed: 37295336
DOI: 10.1016/j.ghir.2023.101544 -
Hormone Research in Paediatrics 2024Recombinant human growth hormone (rhGH) therapy effectively increases height in various disorders of childhood growth. However, whether rhGH affects pubertal timing is... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Recombinant human growth hormone (rhGH) therapy effectively increases height in various disorders of childhood growth. However, whether rhGH affects pubertal timing is unclear. We aimed to review systematically published evidence on the effect of rhGH on pubertal timing.
METHODS
Embase, MEDLINE, and Cochrane Library databases were searched until December 2021 on randomized and non-randomized controlled studies of rhGH in children.
RESULTS
Twenty-five articles (n = 1,433 children) were identified, describing 12 randomized and 13 non-randomized controlled studies in children with idiopathic short stature (ISS; 15 studies), small for gestational age (n = 6 studies), chronic renal failure (n = 3), Noonan syndrome (n = 1), and growth hormone deficiency (n = 1). Significant differences in the effects of rhGH on pubertal timing were found by clinical indication. Only among children with ISS, rhGH promoted earlier age at pubertal timing (mean difference = -0.46 years; 95% CI, -0.90 to -0.03; 9 studies; n total = 397) or higher relative risk for pubertal onset during study follow-up (1.26; 95% CI, 1.03 to 1.54; 6 studies; n total = 284).
CONCLUSIONS
Treatment with rhGH appears to promote earlier pubertal timing among children with ISS. Evidence was lacking in children with growth hormone deficiency due to the absence of studies with untreated controls.
Topics: Child; Humans; Human Growth Hormone; Growth Hormone; Body Height; Growth Disorders; Dwarfism, Pituitary; Recombinant Proteins
PubMed: 37075730
DOI: 10.1159/000530578 -
Endocrine Jun 2024The separation between the inside and outside through the skin was fundamental for the evolution of prevertebrates, which grow through extrapituitary circuits, to...
PURPOSE
The separation between the inside and outside through the skin was fundamental for the evolution of prevertebrates, which grow through extrapituitary circuits, to vertebrates, which grow through the somatotrophic axis, namely pituitary growth hormone (GH). and circulating IGF1.Individuals with untreated isolated growth hormone (GH) deficiency (IGHD) due to a mutation in the GH-releasing hormone receptor (GHRH) gene, residing in Itabaianinha, Brazil, are vulnerable to skin cancer and have reduced sweating. However other aspects of their skin physiology are still unknown. Our objectives were to evaluate the number of skin cancers, skin aging, and functional aspects of the skin in this IGHD cohort.
METHODS
Twenty-six IGHD individuals and 26 controls matched by age, sex, ethnicity, and occupation were submitted to a biochemical, dermatological and a functional skin assessment by the Multi Probe Adapter Cutometer® MPA 580.
RESULTS
There was no difference in the number of skin cancers and in the degrees of photodamage between the groups. The melanin content in the forearm was similar between the groups but was lower in the buttocks (p = 0.005), as well as skin resistance (p < 0.0001) and elasticity (p = 0.003), lower in the IGHD. There was no difference in hydration and sebum content between the two groups.
CONCLUSION
IGHD is apparently associated with a neutral profile in terms of skin cancer and photodamage, with similar melanin on the forearm and lower buttocks, lower skin resistance and elasticity, with hydration and sebum similar to controls.
Topics: Humans; Male; Female; Adult; Skin; Human Growth Hormone; Middle Aged; Skin Neoplasms; Skin Aging; Young Adult; Skin Physiological Phenomena; Dwarfism, Pituitary; Adolescent
PubMed: 38703329
DOI: 10.1007/s12020-024-03840-1 -
Endocrine Sep 2023The shoulder is the most mobile joint in the entire human body. During arm elevation, it requires the integrity of a set of muscles, bones, and tendons. Individuals with...
OBJECTIVES
The shoulder is the most mobile joint in the entire human body. During arm elevation, it requires the integrity of a set of muscles, bones, and tendons. Individuals with short stature often need to raise their arms above the shoulder girdle and may have functional restriction or shoulder injuries. The impact of isolated GH deficiency (IGHD) on joints remains not well defined. The purpose of this work is to evaluate the function and structure of the shoulder in short-statured adult individuals with untreated IGHD due to the same homozygous mutation in the GHRH receptor gene.
METHODS
A cross-sectional study (evidence 3) was carried out in 20 GH-naive IGHD subjects and 20 age-matched controls. They completed the disabilities of the arm, shoulder, and hand (DASH) questionnaire and shoulder ultrasound (US). Thickness of the anterior, medial, and posterior portions of the supraspinatus tendon and of subacromial space was measured, and the number of individuals with tendinosis or tearing of the supraspinatus tendon was registered.
RESULTS
DASH score was similar between IGHD and controls, but IGHD subjects complained less of symptoms (p = 0.002). The number of individual with tears was higher in the controls (p = 0.02). As expected, the absolute US measurements were lower in IGHD, but the magnitude of the reduction was most pronounced in the thickness of the anterior portion of the supraspinatus tendon.
CONCLUSION
Adults with lifetime IGHD do not have functional shoulder restrictions, complain less of problems in performing upper extremity activities, and have fewer tendinous injuries than controls.
Topics: Adult; Humans; Dwarfism, Pituitary; Shoulder; Cross-Sectional Studies; Hypopituitarism; Growth Hormone
PubMed: 37198380
DOI: 10.1007/s12020-023-03391-x -
Pituitary Oct 2023To analyze the clinical, hormonal, and radiological characteristics of Pituitary stalk interruption syndrome (PSIS) in children with growth hormone deficiency (GHD).
PURPOSE
To analyze the clinical, hormonal, and radiological characteristics of Pituitary stalk interruption syndrome (PSIS) in children with growth hormone deficiency (GHD).
METHODS
This is a prospective cross-sectional study, conducted over a period of three years in a short stature clinic of tertiary care referral hospital. 57 severe short stature children with proven GHD were included in the study.
RESULTS
Among 57 children with GHD, 14 (24%) were diagnosed as PSIS. The mean age at diagnosis was 11.8 ± 2.6years. The male to female ratio was 2.5:1. Nine (64%) children had multiple pituitary hormone deficiency (MPHD) and 5 (36%) had isolated growth hormone deficiency (IGHD). In spite of absent or ectopic posterior pituitary (EPP)in Magnetic Resonance Imaging (MRI) of PSIS cohorts, only one had Arginine vasopressin (AVP) deficiency. EPP was seen near median eminence in 6 (44%), elsewhere in 4 (28%), and absent in 4 (28%)children. The height gain following growth hormone therapy was better in PSIS cohorts as compared to non-PSIS.
CONCLUSION
Male gender, breech presentation, external congenital anomalies like cryptorchidism, midline defects and nystagmus were more common in children with PSIS. MPHD were more frequently seen in PSIS whereas IGHD in non-PSIS cohort. AVP deficiency is very rare in PSIS despite of absent or ectopic posterior pituitary in MRI. High index of clinical suspicion in all severe short stature may lead to early diagnosis and prompt initiation of growth hormone treatment for better outcome.
Topics: Adolescent; Child; Female; Humans; Male; Cross-Sectional Studies; Dwarfism, Pituitary; Growth Hormone; Human Growth Hormone; Hypopituitarism; Magnetic Resonance Imaging; Pituitary Gland; Pituitary Hormones; Prospective Studies
PubMed: 37695468
DOI: 10.1007/s11102-023-01351-2