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1.
Osteoporos Int ; 35(2): 327-338, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37872346

RESUMEN

Glucocorticoid use in Duchenne and Becker muscular dystrophy prolongs ambulation but cause significant skeletal toxicity. Our analysis has immediate clinical implications, suggesting that growth hormone and testosterone have a stronger effect prior to first and subsequent vertebral fracture, respectively, relative to bisphosphonates alone in children with dystrophinopathies on chronic glucocorticoids. PURPOSE: Glucocorticoids prolong ambulation in boys with Duchenne muscular dystrophy; however, they have significant endocrine side effects. We assessed the impact of growth hormone (GH), testosterone, and/or zoledronic acid (ZA) on vertebral fracture (VF) incidence in patients with dystrophinopathies on chronic glucocorticoids. METHODS: We conducted a longitudinal retrospective review of 27 males with muscular dystrophy. Accelerated failure time (AFT) models were used to estimate the relative time to VF while on GH, testosterone, and/or ZA compared to ZA alone. Results are reported as failure time ratio, where >1 indicates prolonged time versus <1 indicates shorter time to next VF. RESULTS: The prevalence of growth impairment was 96% (52% utilized GH), pubertal delay was 86% (72% utilized testosterone), and low trauma fractures were 87% (72% utilized ZA). Multivariable analysis of the AFT models showed that participants on either GH or testosterone treatment relative to ZA alone experienced prolonged time to next VF (1.253, P<0.001), with GH being the significant contributor when analyzed independently from testosterone (1.229, P<0.001). Use of ZA with GH or testosterone relative to ZA alone resulted in prolonged time to next VF (1.171, P<0.001), with testosterone being a significant contributor (1.130, P=0.033). CONCLUSION: GH and testosterone each decreased VF risk in patients independent of or in combination with ZA, respectively.


Asunto(s)
Distrofia Muscular de Duchenne , Fracturas de la Columna Vertebral , Masculino , Niño , Humanos , Fracturas de la Columna Vertebral/epidemiología , Fracturas de la Columna Vertebral/etiología , Fracturas de la Columna Vertebral/tratamiento farmacológico , Glucocorticoides/efectos adversos , Testosterona/efectos adversos , Hormona del Crecimiento/efectos adversos , Distrofia Muscular de Duchenne/complicaciones , Distrofia Muscular de Duchenne/tratamiento farmacológico , Ácido Zoledrónico/uso terapéutico
2.
Best Pract Res Clin Endocrinol Metab ; 37(6): 101788, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37308376

RESUMEN

Daily administration of growth hormone (GH) treatment has been in clinical use for treatment for GH deficiency (GHD) in adults for more than 30 years. Numerous studies have demonstrated evidence that GH treatment improves body composition, cardiovascular risk factors and quality of life with few side effects. Less frequent GH injections are hypothesized to improve adherence and several long-acting GH (LAGH) formulations have been developed and a few have been approved and marketed. Different pharmacological modifications have been applied and the pharmacokinetics and pharmacodynamics of LAGH are different to each other and to those of daily injections and require different dosing and monitoring specific for each LAGH. Studies have shown improved adherence with LAGH, and short-term efficacy and side effects are comparable between daily GH injections and LAGHs. Long-term treatment with daily GH injections is effective and safe, while long-term studies for LAGHs are awaited. In this review challenges, benefits, and risks of treatment with daily and long-acting GH preparations will be compared.


Asunto(s)
Enanismo Hipofisario , Hormona de Crecimiento Humana , Hipopituitarismo , Adulto , Humanos , Hormona del Crecimiento/efectos adversos , Calidad de Vida , Hormona de Crecimiento Humana/efectos adversos , Enanismo Hipofisario/tratamiento farmacológico , Enanismo Hipofisario/inducido químicamente
3.
BMC Pediatr ; 22(1): 371, 2022 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-35764954

RESUMEN

BACKGROUND: The growth potential in pubertal boys with short stature is limited by the effect of estrogen on epiphyseal fusion. This study aims to identify the efficacy and safety of the combination of growth hormone (GH) and letrozole on adult height (AH) in pubertal boys with short stature. METHODS: This is a retrospective record based study. Pubertal boys with short stature who were treated with GH and letrozole were followed up at outpatient clinics in our hospital. Twenty subjects who reached AH are reported here. RESULTS: Baseline chronological age was 12.12 ± 1.14 yr and bone age was 13.00 ± 0.93 yr. The period of GH/letrozole treatment was 1.94 ± 0.67 yr. Height standard deviation score for bone age was increased from -1.46 ± 0.51 before treatment to -0.12 ± 0.57 after treatment (P < 0.001). The predicted AH before treatment, predicted AH after treatment, AH, and genetic target height were 161.02 ± 4.12 cm, 172.11 ± 4.20 cm, 172.67 ± 2.72 cm, and 167.67 ± 3.56 cm, respectively. There was a significant predicted AH difference before and after treatment (P < 0.001). There was a significant difference between predicted AH before treatment and genetic target height (P < 0.001). Predicted AH after therapy was higher than that of gene target height (P < 0.001), as well as AH and genetic target height (P < 0.001). There was no significant side effect. CONCLUSIONS: GH and letrozole combination can enhance AH in pubertal boys with short stature.


Asunto(s)
Enanismo , Hormona de Crecimiento Humana , Adulto , Hormona del Crecimiento/efectos adversos , Registros de Hospitales , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Letrozol/uso terapéutico , Masculino , Estudios Retrospectivos
4.
Dermatol Online J ; 28(1)2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-35499415

RESUMEN

A wide variety of medications have been associated with lichenoid drug eruption. They present similarly or even identically to idiopathic lichen planus, both clinically and histologically. Lichenoid eruption has been associated with recombinant human growth hormone intake in two previous patients. Herein, we describe a young boy who developed a lichenoid eruption following growth hormone injection for dwarfism.


Asunto(s)
Enanismo , Hormona de Crecimiento Humana , Liquen Plano , Erupciones Liquenoides , Niño , Enanismo/complicaciones , Enanismo/tratamiento farmacológico , Hormona del Crecimiento/efectos adversos , Hormona de Crecimiento Humana/efectos adversos , Humanos , Liquen Plano/patología , Erupciones Liquenoides/inducido químicamente , Erupciones Liquenoides/patología , Masculino
5.
BMC Endocr Disord ; 21(1): 243, 2021 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-34893062

RESUMEN

BACKGROUND: Short stature is the most consistent characteristic feature of Turner syndrome (TS). To improve final heights of children with TS effectively, it is important to provide them with early and appropriate treatment using growth hormone (GH). The objective of this study was to assess the efficacy and safety of a new recombinant human GH, Growtropin®-II (DA-3002, Dong-A ST Co., Ltd) versus a comparator (Genotropin®, Pfizer Inc.) for Korean children with TS. METHODS: This open-label, active-controlled, parallel-group, randomized controlled phase III trial was conducted at 11 hospitals in Korea. Eligible patients (n = 58) were randomized to two groups: 1) DA-3002 group (administrated with DA-3002 at 0.14 IU [0.0450-0.050 mg] /kg/day); and 2) comparator group (administrated with the comparator at 0.14 IU [0.0450-0.050 mg] /kg/day). RESULTS: The change from baseline in annualized height velocity (HV) after a 52-week treatment period was 4.15 ± 0.30 cm/year in the DA-3002 group and 4.34 ± 0.29 cm/year in the comparator group. The lower bound of 95% two-sided confidence interval for group difference in the change of annualized HV (- 1.02) satisfied the non-inferiority margin (- 1.5). The change in height standard deviation score (HtSDS) at 52-week was 0.70 ± 0.23 for the DA-3002 group and 0.66 ± 0.39 for the comparator group, showing no significant (p = 0.685) difference between the two groups. The change of skeletal maturity defined as change in bone age/change in chronological age between the two groups was not significantly different (1.25 ± 0.58 for the DA-3002 group and 1.47 ± 0.45 for the comparator group, p = 0.134). Changes from baseline in serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) after 52 weeks of treatment did not differ significantly between the two groups (p = 0.565 and p = 0.388, respectively) either. The occurrence of adverse events was not statistically different between groups. CONCLUSIONS: This study demonstrates that the efficacy and safety of GH treatment with DA-3002 in children with TS are comparable with those of the comparator. It is expected to analysis the long-term effect of DA-3002 on the increase of final adult height in children with TS and possible late-onset complications in the future. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov. ClinicalTrials.gov identifier: NCT01813630 (19/03/2013).


Asunto(s)
Estatura/efectos de los fármacos , Hormona del Crecimiento/farmacología , Terapia de Reemplazo de Hormonas , Síndrome de Turner/tratamiento farmacológico , Niño , Preescolar , Femenino , Hormona del Crecimiento/administración & dosificación , Hormona del Crecimiento/efectos adversos , Humanos , Proteínas Recombinantes , República de Corea
6.
Aging Cell ; 20(12): e13505, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34811875

RESUMEN

Somatopause refers to the gradual declines in growth hormone (GH) and insulin-like growth factor-1 throughout aging. To define how induced somatopause affects skeletal integrity, we used an inducible GH receptor knockout (iGHRKO) mouse model. Somatopause, induced globally at 6 months of age, resulted in significantly more slender bones in both male and female iGHRKO mice. In males, induced somatopause was associated with progressive expansion of the marrow cavity leading to significant thinning of the cortices, which compromised bone strength. We report progressive declines in osteocyte lacunar number, and increases in lacunar volume, in iGHRKO males, and reductions in lacunar number accompanied by ~20% loss of overall canalicular connectivity in iGHRKO females by 30 months of age. Induced somatopause did not affect mineral/matrix ratio assessed by Raman microspectroscopy. We found significant increases in bone marrow adiposity and high levels of sclerostin, a negative regulator of bone formation in iGHRKO mice. Surprisingly, however, despite compromised bone morphology, osteocyte senescence was reduced in the iGHRKO mice. In this study, we avoided the confounded effects of constitutive deficiency in the GH/IGF-1 axis on the skeleton during growth, and specifically dissected its effects on the aging skeleton. We show here, for the first time, that induced somatopause compromises bone morphology and the bone marrow environment.


Asunto(s)
Composición Corporal/fisiología , Enfermedades Óseas Metabólicas/fisiopatología , Hormona del Crecimiento/efectos adversos , Espectrometría Raman/métodos , Envejecimiento , Animales , Femenino , Masculino , Ratones
8.
Retin Cases Brief Rep ; 15(6): 789-794, 2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-31568222

RESUMEN

PURPOSE: To report the correlation between recombinant growth hormone (rhGH) dosage and retinal nerve fiber layer (RNFL) thickness values measured by optical coherence tomography in a case of pseudotumor cerebri syndrome (PTCS) after rhGH. METHODS: An 11-year-old girl was receiving rhGH for panhypopituitarism. The patient developed PTCS, and her rhGH dose was adjusted using optical coherence tomography RNFL thickness measurements. The linear correlation coefficient (r) and coefficient of determination (r2) were calculated to assess the relationship between RNFL thickness and rhGH dose. RESULTS: As the rhGH dosage was increased, the RNFL thickness values also increased, especially when acetazolamide was excluded because of its confounding effect. (r = 0.64) In separate subgroup analysis, a higher acetazolamide dosage strongly correlated with reduced RNFL thickness (r = 0.77). CONCLUSION: Although PTCS is a rare complication after rhGH therapy, its detrimental effects cannot be ignored. In our case report, we used optical coherence tomography RNFL values in addition to clinical findings to carefully titrate the rhGH dosage to prevent a flare-up of PTCS. Despite the obvious need for larger studies, our case report shows the value of RNFL thickness measured by optical coherence tomography and the valuable additional data it provides to refine rhGH therapy as an adjunct noninvasive method in PTCS.


Asunto(s)
Hormona del Crecimiento , Seudotumor Cerebral , Tomografía de Coherencia Óptica , Niño , Femenino , Hormona del Crecimiento/administración & dosificación , Hormona del Crecimiento/efectos adversos , Humanos , Fibras Nerviosas , Seudotumor Cerebral/inducido químicamente , Seudotumor Cerebral/diagnóstico por imagen , Células Ganglionares de la Retina
10.
J Clin Res Pediatr Endocrinol ; 13(1): 104-108, 2021 02 26.
Artículo en Inglés | MEDLINE | ID: mdl-32349463

RESUMEN

Fibroma of tendon sheath (FTS) is an uncommon mass that arises from the tendon sheath of extremities. The tumor typically affects adults between ages 20 and 50 years with a predominance in males. To date, growth hormone (GH) treatment is safe for children with Turner syndrome without risk factors and is accepted worldwide. This article reports the case of a nine-year-old female patient with Turner syndrome and FTS during GH treatment. She had been treated with daily subcutaneous GH to improve growth failure with a mean dose of 0.28 mg/kg/week and the level of insulin-like growth factor-1 was within the normal range. During the follow-up period, she complained about a mass in her hand, subsequently diagnosed as FTS. This report illustrates the clinical impact of Turner syndrome and GH treatments on the occurrence of this tumor through literature reviews. Further studies are needed to highlight the association between FTS and GH treatment, especially in Turner syndrome.


Asunto(s)
Fibroma/inducido químicamente , Hormona del Crecimiento/efectos adversos , Mano/patología , Tendones/patología , Síndrome de Turner/tratamiento farmacológico , Niño , Femenino , Hormona del Crecimiento/administración & dosificación , Humanos
12.
Yonsei Med J ; 61(4): 331-340, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32233176

RESUMEN

PURPOSE: Osteoarthritis (OA) of the temporomandibular joint (TMJ) elicits cartilage and subchondral bone defects. Growth hormone (GH) promotes chondrocyte growth. The aim of this study was to evaluate the efficacy of intra-articular injections of GH to treat TMJ-OA. MATERIALS AND METHODS: Monosodium iodoacetate (MIA) was used to induce OA in the TMJs of rats. After confirming the induction of OA, recombinant human GH was injected into the articular cavities of rats. Concentrations of GH and IGF-1 were measured in the blood and synovial fluid, and OA grades of cartilage and subchondral bone degradation were recorded by histological examination and micro-computed tomography. RESULTS: MIA-induced OA in the rat TMJ upregulated insulin-like growth factor-1 (IGF-1) rather than GH levels. GH and IGF-1 concentrations were increased after local injection of GH, compared with controls. Locally injected GH lowered osteoarthritic scores in the cartilage and subchondral bone of the TMJ. CONCLUSION: Intra-articular injection of GH improved OA scores in rat TMJs in both cartilage and subchondral bone of the condyles without affecting condylar bone growth. These results suggest that intra-articular injection of human GH could be a suitable treatment option for TMJ-OA patients in the future.


Asunto(s)
Condrocitos/efectos de los fármacos , Hormona del Crecimiento/administración & dosificación , Factor I del Crecimiento Similar a la Insulina/administración & dosificación , Osteoartritis/tratamiento farmacológico , Articulación Temporomandibular/efectos de los fármacos , Anciano , Animales , Cartílago Articular/diagnóstico por imagen , Cartílago Articular/patología , Hormona del Crecimiento/efectos adversos , Hormona de Crecimiento Humana , Humanos , Inyecciones Intraarticulares , Masculino , Osteoartritis/diagnóstico por imagen , Osteoartritis/patología , Ratas , Líquido Sinovial , Articulación Temporomandibular/diagnóstico por imagen , Articulación Temporomandibular/fisiopatología , Microtomografía por Rayos X
13.
ESC Heart Fail ; 6(6): 1216-1221, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31696666

RESUMEN

AIMS: Although preliminary studies have demonstrated safety and effectiveness of single replacement therapy for growth hormone deficiency or testosterone deficiency in heart failure (HF), no data are available regarding the combined treatment with both GH and T in this setting. Thus, the aim of the present hypothesis generating pilot study was to evaluate the effectiveness and safety of multiple hormonal replacement therapies in chronic HF. METHODS AND RESULTS: Five stable HF with reduced ejection fraction patients, with a concomitant diagnosis of growth hormone deficiency and testosterone deficiency, on top of guideline-based HF treatment underwent 1 year of GH replacement therapy by subcutaneous injections of somatotropin at a dose of 0.012 mg/kg every second day. After 12 months, a T replacement treatment was added at a dosage of 1000 mg every 3 months. Each patient underwent a complete M-mode, two-dimensional, and Doppler echocardiographic examination, and an incremental symptom-limited cardiopulmonary exercise test on a bicycle ergometer at baseline (BL), after 1 year of GH treatment (V1), and after 1 year of combined GH + T treatments (V2). One-year of GH treatment resulted in a significant improvement in left ventricular ejection fraction (+5.4%, P < 0.01), New York Heart Association functional class (P < 0.05), and peak oxygen consumption (VO2 peak) (+19.3%, P < 0.01), and in a significant reduction in NT-proBNP levels (-35.1%, P < 0.01). Notably, one additional year of combined GH and T replacement therapy induced a further increase in VO2 peak (+27.7%, final delta change + 52.44%, P < 0.01), as well as a significant improvement in muscular strength, as assessed by handgrip dynamometry (+17.5%, final delta change + 25.8%, P < 0.01). These beneficial effects were paralleled with an improvement of the overall clinical status (as assessed by New York Heart Association class). Of note, neither adverse effects nor cardiovascular events were reported during the follow-up period. CONCLUSIONS: Our preliminary data suggest for the first time that combined replacement therapy with GH and T could be considered safe and therapeutic in HF patients with multiple hormone deficiencies, supporting the hypothesis that multiple hormone deficiencies syndrome can be considered as a novel and promising therapeutic target in HF. Further studies with a more robust design and larger population are needed.


Asunto(s)
Hormona del Crecimiento , Insuficiencia Cardíaca/tratamiento farmacológico , Terapia de Reemplazo de Hormonas , Testosterona , Anciano , Hormona del Crecimiento/administración & dosificación , Hormona del Crecimiento/efectos adversos , Hormona del Crecimiento/deficiencia , Hormona del Crecimiento/uso terapéutico , Humanos , Persona de Mediana Edad , Consumo de Oxígeno/fisiología , Proyectos Piloto , Volumen Sistólico/fisiología , Testosterona/administración & dosificación , Testosterona/efectos adversos , Testosterona/deficiencia , Testosterona/uso terapéutico
14.
Rom J Morphol Embryol ; 60(2): 653-658, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31658340

RESUMEN

Craniofacial and dental morphology is influenced by different circulating hormones, but it is of particular importance that there is growth hormone (GH) in normal craniofacial and teeth development. Craniofacial morphometry studies in children with GH deficiency show different changes in certain anthropometric variables in the sense of reducing their values compared to normal children's developmental norms in different stages of childhood and adolescence. Therefore, the early establishment of GH replacement therapy can correct craniofacial morphological changes induced by GH deficiency. In our study, we evaluated different anthropometric craniofacial variables at children with GH deficiency and we established some anthropometric and morphological characteristics associated with this pathology.


Asunto(s)
Cefalometría/métodos , Hormona del Crecimiento/efectos adversos , Hormona del Crecimiento/deficiencia , Adolescente , Niño , Femenino , Humanos , Masculino
15.
Sleep Med ; 64: 23-29, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31655321

RESUMEN

OBJECTIVE: Imprinting disorders (ID), such as Prader-Willi syndrome (PWS), are associated with sleep-disordered breathing (SDB). No data are available for Silver-Russell syndrome (SRS), another ID that shares clinical features with PWS, although many patients describe excessive daytime sleepiness, disturbed sleep, and snoring. The aim of this study was to characterize sleep in children with SRS and to evaluate the impact of recombinant growth hormone (rGH) therapy. METHODS: We performed a retrospective analysis of sleep recordings in 40 patients with molecularly proven SRS (methylation anomaly in 11p15 [n = 32] or maternal uniparental disomy of chromosome 7 [n = 16]). Sleep recordings were either by means of polygraphy or polysomnography (PSG) (n = 16). A total of 34 patients received rGH therapy. RESULTS: We collected 61 sleep recordings. The mean apnea-hypopnea index (AHI) was 3.4 events/h (0-12.4), with a mean central AHI of 0.5 events/h (0-2.4). SDB was identified in 73.8% (n = 45) of the recordings and was severe in 4.9%. SDB was present in 86.4% of patients before rGH therapy and was severe in 13.6%. AHI worsened for 5 of 12 patients with sleep recordings before and after rGH therapy initiation, reaching mild impairment. The mean rGH dose was 32.3 µg/kg/(12.9-51.4), with a mean insulin-like growth factor 1 plasma level of 1.7 SDS (-1.9 to 6.6). CONCLUSION: Most patients with SRS present with SDB with an obstructive profile, possibly explained by narrowing of the airways and lymphoid organ hypertrophy. We recommend systematic ear-nose-throat evaluation of SRS patients and PSG if there are clinical anomalies, preferably before initiating rGH therapy, to monitor and adapt the management of patients with SDB.


Asunto(s)
Hormona del Crecimiento/uso terapéutico , Síndrome de Silver-Russell/diagnóstico , Síndrome de Silver-Russell/tratamiento farmacológico , Síndromes de la Apnea del Sueño/diagnóstico , Niño , Preescolar , Femenino , Hormona del Crecimiento/efectos adversos , Humanos , Masculino , Polisomnografía , Estudios Retrospectivos , Síndrome de Silver-Russell/complicaciones , Síndromes de la Apnea del Sueño/complicaciones , Resultado del Tratamiento
16.
Am J Case Rep ; 20: 689-696, 2019 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-31086127

RESUMEN

BACKGROUND Growth hormone insensitivity and reduced levels of insulin-like growth factor-1 (IGF-1) are associated with metabolic syndrome that includes obesity, hyperglycemia, type 2 diabetes mellitus, and dyslipidemia. Laron syndrome is a rare autosomal recessive condition associated with insensitivity to growth hormone that results in short stature and metabolic syndrome and is usually diagnosed in childhood. This report is of a 42-year-old Mexican woman with untreated growth hormone insensitivity and diabetic retinopathy, in whom gene sequencing supported the identification of a variant of Laron syndrome. CASE REPORT A 42-year-old Mexican woman with untreated growth hormone insensitivity, metabolic syndrome, and type 2 diabetes mellitus was diagnosed with cataracts, severe retinopathy and hearing loss. She was investigated for genetic causes of reduction in IGF-1. Next-generation sequencing (NGS) showed genetic changes in the growth hormone and IGF-1 axis. The patient's phenotype and genetic changes were consistent with Laron syndrome. CONCLUSIONS The early detection of reduced IGF-1 and identification of the cause of growth hormone insensitivity require international consensus on the approach to diagnosis and treatment methods, including effective IGF-1 replacement therapy. Early diagnosis may reduce the clinical consequences of complications that include short stature the development of metabolic syndrome, type 2 diabetes mellitus, and retinopathy.


Asunto(s)
Retinopatía Diabética/etiología , Hipersensibilidad a las Drogas/etiología , Hormona del Crecimiento/efectos adversos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Síndrome de Laron/diagnóstico , Adulto , Retinopatía Diabética/diagnóstico , Hipersensibilidad a las Drogas/diagnóstico , Femenino , Humanos , Síndrome de Laron/complicaciones
17.
Clin Endocrinol (Oxf) ; 91(1): 118-123, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30973645

RESUMEN

OBJECTIVE: Some features of subjects with Prader-Willi syndrome (PWS) resemble those seen in growth hormone deficiency (GHD). Children with PWS are treated with growth hormone (GH), which has substantially changed their phenotype. Currently, young adults with PWS must discontinue GH after attainment of adult height when they do not fulfil the criteria of adult GHD. Limited information is available about the prevalence of GHD in adults with PWS. This study aimed to investigate the GH/insulin-like growth factor (IGF-I) axis and the prevalence of GHD in previously GH-treated young adults with PWS. DESIGN: Cross-sectional study in 60 young adults with PWS. MEASUREMENTS: Serum IGF-I and IGFBP-3 levels, GH peak during combined growth hormone-releasing hormone (GHRH)-arginine stimulation test. RESULTS: Serum IGF-I was <-2 standard deviation scores (SDS) in 2 (3%) patients, and IGFBP-3 was within the normal range in all but one patient. Median (IQR) GH peak was 17.8 µg/L (12.2; 29.7) [~53.4 mU/L] and below 9 µg/L in 9 (15%) patients. Not one patient fulfilled the criteria for adult GHD (GH peak < 9 µg/L and IGF-I < -2 SDS), also when BMI-dependent criteria were used. A higher BMI and a higher fat mass percentage were significantly associated with a lower GH peak. There was no significant difference in GH peak between patients with a deletion or a maternal uniparental disomy (mUPD). CONCLUSIONS: In a large group of previously GH-treated young adults with PWS, approximately 1 in 7 exhibited a GH peak <9 µg/L during a GHRH-arginine test. However, none of the patients fulfilled the consensus criteria for adult GHD.


Asunto(s)
Enanismo Hipofisario/sangre , Enanismo Hipofisario/epidemiología , Hormona del Crecimiento/uso terapéutico , Síndrome de Prader-Willi/sangre , Síndrome de Prader-Willi/tratamiento farmacológico , Adulto , Índice de Masa Corporal , Estudios Transversales , Enanismo Hipofisario/etiología , Femenino , Hormona del Crecimiento/efectos adversos , Hormona de Crecimiento Humana/sangre , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Prevalencia , Adulto Joven
18.
Endocrine ; 63(3): 497-506, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30617738

RESUMEN

PURPOSE: Growth hormone (GH) replacement decreases insulin sensitivity in healthy individuals. However, the effects of GH on organ-specific insulin sensitivity and glucose effectiveness are not well characterized. The purpose of this study was to evaluate the effects of GH administration for 26 weeks on muscle and hepatic insulin sensitivity and glucose effectiveness in healthy older individuals. METHODS: This report is from a 26-week randomized, double-blind, placebo-controlled parallel-group trial in healthy, ambulatory, community-dwelling older women and men. We compared surrogate indices of insulin sensitivity [quantitative insulin-sensitivity check index (QUICKI), muscle insulin sensitivity index (MISI), hepatic insulin resistance index (HIRI)] and glucose effectiveness [oral glucose effectiveness index (oGE)] derived from oral glucose tolerance tests (OGTTs) in subjects before and after 26 weeks of administration of GH (n = 17) or placebo (n = 15) as an exploratory outcome. RESULTS: GH administration for 26 weeks significantly increased fasting insulin concentrations and HIRI but did not significantly change MISI or oGE compared to placebo. CONCLUSIONS: GH administration for 26 weeks in healthy older subjects impairs insulin sensitivity in the liver but not skeletal muscle and does not alter glucose effectiveness.


Asunto(s)
Hormona del Crecimiento/efectos adversos , Terapia de Reemplazo de Hormonas/efectos adversos , Resistencia a la Insulina , Hígado/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Masculino
19.
Endocr Rev ; 40(2): 558-574, 2019 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-30500870

RESUMEN

Several components of the GH axis are involved in tumor progression, and GH-induced intracellular signaling has been strongly associated with breast cancer susceptibility in genome-wide association studies. In the general population, high IGF-I levels and low IGF-binding protein-3 levels within the normal range are associated with the development of common malignancies, and components of the GH-IGF signaling system exhibit correlations with clinical, histopathological, and therapeutic parameters in cancer patients. Despite promising findings in preclinical studies, anticancer therapies targeting the GH-IGF signaling system have led to disappointing results in clinical trials. There is substantial evidence for some degree of protection against tumor development in several animal models and in patients with genetic defects associated with GH deficiency or resistance. In contrast, the link between GH excess and cancer risk in acromegaly patients is much less clear, and cancer screening in acromegaly has been a highly controversial issue. Recent studies have shown that increased life expectancy in acromegaly patients who attain normal GH and IGF-I levels is associated with more deaths due to age-related cancers. Replacement GH therapy in GH deficiency hypopituitary adults and short children has been shown to be safe when no other risk factors for malignancy are present. Nevertheless, the use of GH in cancer survivors and in short children with RASopathies, chromosomal breakage syndromes, or DNA-repair disorders should be carefully evaluated owing to an increased risk of recurrence, primary cancer, or second neoplasia in these individuals.


Asunto(s)
Acromegalia/metabolismo , Hormona del Crecimiento/metabolismo , Hipopituitarismo/metabolismo , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Síndrome de Laron/metabolismo , Neoplasias/metabolismo , Transducción de Señal , Acromegalia/tratamiento farmacológico , Adulto , Animales , Niño , Hormona del Crecimiento/efectos adversos , Hormona del Crecimiento/deficiencia , Humanos , Neoplasias/inducido químicamente , Neoplasias/prevención & control
20.
Acta amaz ; 48(3): 197-206, July-Sept. 2018. tab, graf
Artículo en Inglés | LILACS, VETINDEX | ID: biblio-1455367

RESUMEN

Colossoma macropomum, known locally as tambaqui, is the native fish most farmed in Brazil, however, technological advances are needed to reach efficient production rates. Modulating growth factors, such as growth hormone, may be associated with improved growth rate and feed efficiency. The use of exogenous hormone for fish rearing is prohibited in Brazil, yet the experimental use of bovine hormone can be useful in research aimed at understanding how to stimulate endogenous growth hormones in fish. Therefore, the present study had the strict objective of understanding the effects of growth hormone on the physiology and zootechnical parameters of C. macropomum under experimental conditions. The animals were intraperitoneally injected every fifteen days with 1, 10 and 100 g g-1 of bGH using 0.9% NaCl saline as diluent. The 10 and 100 g g-1 bolus had a positive effect on the performance indexes of C. macropomum: weight gain (g), growing length (cm), daily weight gain (g), feed conversion and specific growth rate (% per day). The bGH promoted a greater increase in length than in mass, which caused a reduction in condition factor of the individuals receiving a bolus of 10 and 100 g g-1. Furthermore, bGH caused no changes in glucose levels, cortisol, hematological parameters, plasma levels of Na+ and K+, and activity of gills H+-ATPase and Na+, K+-ATPase, at least during the experimental period considered in the present study.


O tambaqui, Colossoma macropomum, é o peixe nativo mais cultivado no Brasil. No entanto, avanços tecnológicos são necessários para incrementar as taxas de produção. Fatores de crescimento moduladores, como o hormônio do crescimento, podem estar associados a uma melhoria na taxa de crescimento e eficiência alimentar. O uso de hormônio exógeno para a criação de peixes é proibido por lei no Brasil, porém, o uso experimental do hormônio bovino pode ser útil em pesquisas que visam determinar mecanismos de estímulo dos hormônios de crescimento endógenos em peixes. Portanto, o presente estudo teve como objetivo estrito a compreensão dos efeitos do hormônio de crescimento sobre a fisiologia e os parâmetros zootécnicos de C. macropomum em condições experimentais . Os animais foram injetados intraperitonealmente a cada quinze dias com 1, 10 e 100 g g-1 de bGH, utilizando solução salina a 0,9% de NaCl como diluente. Observou-se que as concentrações 10 e 100 g g-1 tiveram um efeito positivo sobre os índices de desempenho de C. macropomum em ganho de massa (g), crescimento em comprimento (cm), ganho de massa diário (g), conversão alimentar e taxa de crescimento específico (% por dia). O bGH promoveu ganho maior em comprimento do que em massa, o que causou diminuição do fator de condição nos indivíduos que receberam 10 e 100 g g-1. Além disso, o bGH não causou alterações nos níveis de glicose, cortisol, parâmetros hematológicos, níveis plasmáticos de Na+ e K+ e na atividade de H+-ATPase e Na+, K+-ATPase nas brânquias durante o período experimental.


Asunto(s)
Animales , Characiformes/crecimiento & desarrollo , Characiformes/sangre , Hormona del Crecimiento/efectos adversos , Acuicultura , Osmorregulación
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