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1.
Obesity (Silver Spring) ; 28(11): 2038-2039, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32808459

RESUMO

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.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/sangue , Hormônio do Crescimento Humano/deficiência , Obesidade/sangue , Pneumonia Viral/sangue , Fatores Etários , Idoso , Humanos , Masculino , Pandemias
2.
PLoS One ; 15(7): e0236357, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32687509

RESUMO

Adult growth hormone deficiency (GHD) is being increasingly recognized to cause premature mortality exacerbated by oxidative stress. A case-control observational study has been performed with the primary objective of evaluating new parameters of oxidative stress and macromolecular damage in adult GHD subjects: serum nitrotryptophan; Total Antioxidant Capacity expressed as LAG time; urinary hexanoil-lysine; urinary dityrosine and urinary 8-OH-deoxyguanosine. GHD was diagnosed using Growth Hormone-Releasing Hormone 50µg iv+arginine 0,5 g/Kg test, with a peak GH response <9 µg /L when BMI was <30 kg/m2 or <4 µg/L when BMI was >30 kg/m2. Patients affected by adult GHD were divided into three groups, total GHD (n = 26), partial GHD (n = 25), and controls (n = 29). Total Antioxidant Capacity, metabolic and hormonal parameters have been determined in separate plasma samples; nitrotryptophan in serum samples; hexanoil-lysine, dityrosine, 8-OH-deoxyguanosine in urine samples. Assessment of hexanoil-lysine exhibited a trend to increase in comparing total GHD vs partial and controls, although not significant. Values of 8-OH-deoxyguanosine did not significantly differ among the three groups. Significant lower levels of dityrosine in partial GHD vs total and controls were found. No significant difference in nitrotriptophan serum levels was found, while significantly greater values of Total Antioxidant Capacity were showed in total and partial GHD vs controls. Thus, our result confirm that oxidative stress is increased both in partial and total adult GHD. The lack of compensation by antioxidants in total GHD may be connected to the complications associated to this rare disorder.


Assuntos
Antioxidantes/análise , Hormônio do Crescimento Humano/deficiência , Hipopituitarismo/metabolismo , Síndrome Metabólica/metabolismo , Estresse Oxidativo/fisiologia , 8-Hidroxi-2'-Desoxiguanosina/urina , Adulto , Malformação de Arnold-Chiari/sangue , Malformação de Arnold-Chiari/complicações , Malformação de Arnold-Chiari/metabolismo , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Síndrome da Sela Vazia/sangue , Síndrome da Sela Vazia/complicações , Síndrome da Sela Vazia/metabolismo , Feminino , Humanos , Hipopituitarismo/sangue , Hipopituitarismo/etiologia , Hipopituitarismo/urina , Peroxidação de Lipídeos , Lisina/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/etiologia , Síndrome Metabólica/urina , Pessoa de Meia-Idade , Triptofano/análogos & derivados , Triptofano/sangue , Tirosina/análogos & derivados , Tirosina/urina
4.
Eur J Endocrinol ; 182(6): 559-567, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32337961

RESUMO

Objectives: To report the frequency and characteristics of growth hormone (GH) deficiency (GHD) in adolescents who had normalized GH secretion at mid-puberty and to identify possible factors predictive for GH sufficiency at puberty. Design: Clinical analysis of children affected by GHD at five time points: diagnosis; first year of therapy; intermediate stage of puberty; retesting and end of growth phase. Methods: The study population was 80 children with idiopathic GHD and treated with GH for at least 2 years. Treatment was discontinued at the intermediate stage of puberty. Retesting with an arginine test was performed 12 weeks later. If GH peak at retesting was ≥8 µg/L, the therapy was definitively discontinued, otherwise it was restarted and continued until achievement of near-final height. Results: GH therapy was discontinued in 44 children (55%), and restarted in 36 (45%). No evidence of differences in definitive height and in the delta height between the genetic target and the definitive height was found between the two groups. The only predictive factor for GHD at mid-puberty was the insulin growth factor-1 (IGF-1) level at 1 year of GH treatment. Conclusions: GH secretion should be retested at mid-puberty. Retesting at puberty may reduce potential side effects and minimize costs, without impairing growth potential and final height.


Assuntos
Hormônio do Crescimento Humano/deficiência , Puberdade/metabolismo , Criança , Feminino , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Estudos Retrospectivos
5.
Endocrinol. diabetes nutr. (Ed. impr.) ; 67(2): 78-88, feb. 2020. graf, tab
Artigo em Inglês | IBECS | ID: ibc-187432

RESUMO

Introduction: Protocol for prescribing hormone replacement therapy in isolated growth hormone (GH) deficiency includes magnetic resonance imaging of the brain. There is controversy on the frequency of structural pituitary abnormalities and on the importance of abnormal MRI findings on prognosis and response to GH replacement. Methods: A descriptive, retrospective study of children of both sexes aged 0-14 years, who had undergone brain MRI, diagnosed with isolated GH deficiency at a tertiary hospital in the past 14 years, aimed at reporting the frequency of abnormal MRI findings in isolated GH deficiency, and to establish whether differences exist in height diagnosis and evolution according to MRI findings. MRI findings were also compared with the findings reported in healthy children in order to establish incidence. Results: 96 patients were studied, of whom 74/96 (77%) reached adult age. Abnormal MRI findings were seen in 11.5% of them (8/11 of pituitary origin). No brain or pituitary tumor was seen in any case. Patients with abnormal images had a mean age at treatment start of 8 years, a target height of -0.8SD, and a final height of 1.04SD, while patients with normal MRI findings had an age at treatment start of 10 years old, a target height of -1.44SD, and a final height of -1.75SD, with statistically significant differences. Conclusions: Patients with abnormal MRI findings show a more favorable response to GH replacement therapy


Introducción: El protocolo de prescripción de hormona sustitutiva en el déficit aislado de hormona del crecimiento (GH) incluye la realización de una resonancia cerebral. Hay controversia sobre la frecuencia de anomalías hipofisarias y la importancia de los hallazgos anormales de resonancia magnética en el pronóstico y la respuesta al tratamiento de GH. Métodos: Estudio descriptivo retrospectivo de niños de 0 a 14 años, de ambos sexos, con imágenes de resonancia magnética cerebral, que fueron diagnosticados de deficiencia aislada de GH en un hospital terciario en los últimos 14 años, para describir la frecuencia de las anomalías en la resonancia magnética y establecer si existen diferencias en el diagnóstico de talla y evolución de acuerdo con los hallazgos de la resonancia magnética. Además, comparamos los hallazgos en la resonancia con los hallazgos publicados en niños sanos, con el fin de establecer la incidencia. Resultados: Se estudiaron 96 pacientes, alcanzando 74/96 (77%) la edad adulta. El 11,5% tenía imágenes de resonancia magnética anormales (8/11 de origen hipofisario). En ningún caso se observó tumor cerebral o hipofisario. Los pacientes con imágenes anormales mostraron una edad media al inicio de tratamiento de 8 años, talla diana de -0,8 DE y una talla final de 1,04 DE; mientras que los pacientes con imágenes de resonancia magnética normal muestran una edad de inicio de tratamiento de 10 años, una talla diana de -1,44 DE y una talla final de -1,75 DE, con diferencias estadísticamente significativas. Conclusiones: Los pacientes con alteraciones en la resonancia magnética muestran una respuesta más favorable al tratamiento sustitutivo de GH


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Hormônio do Crescimento Humano/deficiência , Cérebro/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Índice de Gravidade de Doença , Hormônio do Crescimento Humano/análise , Estudos Retrospectivos , Estudos Longitudinais , Estatura , Sela Túrcica/diagnóstico por imagem
6.
J Clin Res Pediatr Endocrinol ; 12(1): 71-78, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-31475508

RESUMO

Objective: The aim was to assess growth velocity (GV) during human recombinant growth hormone (hGH) treatment of children with multiple pituitary hormone deficiency (MPHD) caused by pituitary stalk interruption syndrome (PSIS) and to analyze the characteristics of patients that attained normal adult heights. Methods: Data from 74 (16 female) children with MPHD caused by PSIS with GH, thyroid stimulating hormone, gonadotropin and adrenocorticotropic hormone deficiencies were collected. Subjects were divided into groups: 12 pre-pubescent females (Female-Group) and 36 pre-pubescent males (Male-Group 1). The remaining 22 males were further sub-divided into two groups (Male-Group 2 and Male-Group 3) according to the initiation of gonadotropin replacement treatment, based on bone age and height. Results: No differences in change in height standard deviation score (△HtSDS) and GV were observed at different time points of hGH treatment between the Female-Group and Male-Group 1 (p>0.05). GV was significantly greater in the first year of hGH therapy than in subsequent years: Female-Group p=0.011; Male-Group 1 p<0.001; Male-Group 2 p=0.005; and Male-Group 3 p=0.046. Adult height was achieved by 23 (19 males and 4 females) patients. The total gain in height positively correlated with the GV during the first year (r=0.626, p<0.001). Conclusion: GV during hGH treatment were similar amongst pre-pubescent males and females with MPHD caused by PSIS. GV during the first year of hGH treatment appears to be an effective predictor of final height in patients with MPHD caused by PSIS.


Assuntos
Estatura/efeitos dos fármacos , Desenvolvimento Infantil/efeitos dos fármacos , Hormônio do Crescimento Humano/farmacologia , Hipopituitarismo/tratamento farmacológico , Hipófise/anormalidades , Insuficiência Adrenal/tratamento farmacológico , Adulto , Criança , China , Feminino , Seguimentos , Gonadotropinas/deficiência , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/deficiência , Humanos , Hipotireoidismo/tratamento farmacológico , Masculino , Estudos Retrospectivos , Síndrome
7.
Curr Opin Endocrinol Diabetes Obes ; 27(1): 82-86, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31789832

RESUMO

PURPOSE OF REVIEW: To discuss treatments used to enhance growth in pediatric patients with short stature. RECENT FINDINGS: New data confirm the known efficacy of recombinant human growth hormone (rhGH) in growth hormone deficiency (GHD) and idiopathic short stature. The latest data from the Safety and Appropriateness of Growth hormone Treatment in Europe cohort did not indicate a long-term risk of malignancy in those treated for isolated GHD, but possibly increased risk in those with other diagnoses. Recombinant human insulin-like growth factor 1 is effective in treating patients with pregnancy-associated plasma protein A2 deficiency. Gonadotropin-releasing hormone agonists or aromatase inhibitor treatment to delay puberty remains controversial. They are more likely to augment adult height if combined with rhGH treatment in children already receiving rhGH. Preliminary data indicate that recombinant C-type natriuretic peptide (CNP) is safe in children and increases growth velocity upon 42 months of treatment in achondroplasia. SUMMARY: Recent data confirms previous data on rhGH efficacy and safety. Therapies to delay growth plate closure have greatest efficacy to augment height if combined with GH in select diagnoses. Recombinant CNP holds promise as a medical treatment for short stature associated with achondroplasia.


Assuntos
Endocrinologia , Transtornos do Crescimento/prevenção & controle , Transtornos do Crescimento/terapia , Hormônio do Crescimento Humano/deficiência , Adulto , Estatura/efeitos dos fármacos , Criança , Nanismo Hipofisário/tratamento farmacológico , Nanismo Hipofisário/epidemiologia , Endocrinologia/métodos , Endocrinologia/tendências , Europa (Continente)/epidemiologia , Transtornos do Crescimento/epidemiologia , Terapia de Reposição Hormonal/métodos , Terapia de Reposição Hormonal/tendências , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/uso terapêutico , Puberdade/efeitos dos fármacos , Puberdade/fisiologia , Proteínas Recombinantes/uso terapêutico
8.
Sci Rep ; 9(1): 19431, 2019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31857652

RESUMO

To cover increasing energy demands during exercise, tricarboxylic cycle (TCA) flux in skeletal muscle is markedly increased, resulting in the increased formation of intramyocellular acetylcarnitine (AcCtn). We hypothesized that reduced substrate availability within the exercising muscle, reflected by a diminished increase of intramyocellular AcCtn concentration during exercise, might be an underlying mechanism for the impaired exercise performance observed in adult patients with growth hormone deficiency (GHD). We aimed at assessing the effect of 2 hours of moderately intense exercise on intramyocellular AcCtn concentrations, measured by proton magnetic resonance spectroscopy (1H-MRS), in seven adults with GHD compared to seven matched control subjects (CS). Compared to baseline levels AcCtn concentrations significantly increased after 2 hours of exercise, and significantly decreased over the following 24 hours (ANOVA p for effect of time = 0.0023 for all study participants; p = 0.067 for GHD only, p = 0.045 for CS only). AcCtn concentrations at baseline, as well as changes in AcCtn concentrations over time were similar between GHD patients and CS (ANOVA p for group effect = 0.45). There was no interaction between group and time (p = 0.53). Our study suggests that during moderately intense exercise the availability of energy substrate within the exercising muscle is not significantly different in GHD patients compared to CS.


Assuntos
Acetilcarnitina/metabolismo , Exercício Físico/fisiologia , Hormônio do Crescimento Humano/deficiência , Mioblastos/metabolismo , Adiposidade , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo
9.
BMC Endocr Disord ; 19(1): 138, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31829160

RESUMO

BACKGROUND: To evaluate the impact of treatment with recombinant human growth hormone (rhGH; Omnitrope®) on the risk of diabetes mellitus in adults with growth hormone deficiency (GHD), using data from the ongoing PATRO Adults post-marketing surveillance study. METHODS: PATRO Adults is an ongoing post-marketing surveillance study being conducted in hospitals and specialized endocrinology clinics across Europe. All enrolled patients who receive ≥1 dose of Omnitrope® are included in the safety population. Patient profiles, containing all available study database information for each specific patient, were generated for all patients with adverse events (AEs) of diabetes mellitus while participating in the study. Diabetes mellitus was confirmed if fasting plasma glucose was ≥7.0 mmol/L or 2-h plasma glucose ≥11.1 mmol/L during oral glucose tolerance test or glycated hemoglobin ≥6.5%. RESULTS: Up to July 2018, 1293 patients had been enrolled in the study, and 983 (76.0%) remained active. Just under half (n = 687, 49.3%) of the patients were growth hormone (GH) treatment-naïve on entering the study, and most (n = 1128, 87.2%) had multiple pituitary hormone deficiency (MPHD). Diabetes mellitus/inadequate control (worsening) of diabetes mellitus was reported in 21 patients (22 events). The cases were newly diagnosed in 15 patients (age 29-84 years; incidence rate 3.61 per 1000 patient-years) and occurred in 6 patients with pre-existing diabetes mellitus at baseline (age 45-72 years). Most cases of newly diagnosed diabetes mellitus occurred in patients with adult-onset MPHD (n = 13); the remaining cases of new-onset diabetes mellitus occurred in a patient with childhood-onset MPHD who had previously received GH replacement therapy (n = 1), and a patient with adulthood-onset isolated GHD who was naïve to GH replacement therapy (n = 1). All cases of inadequate control/worsening of diabetes mellitus occurred in patients with adult-onset MPHD. CONCLUSIONS: Based on this snapshot of data from PATRO Adults, Omnitrope® treatment is tolerated in adult patients with GHD in a real-life clinical practice setting. No signals of an increased risk for diabetes mellitus have been noted so far, although continued follow-up (both during and after rhGH therapy) is required to confirm this. TRIAL REGISTRATION: Not applicable.


Assuntos
Transtornos do Metabolismo de Glucose/epidemiologia , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Medicamentos Biossimilares , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Europa (Continente)/epidemiologia , Glucose/metabolismo , Hemoglobina A Glicada/análise , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/efeitos adversos , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Hormônios Hipofisários/deficiência , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Fatores de Risco
10.
BMC Endocr Disord ; 19(1): 137, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31829163

RESUMO

BACKGROUND: Body posture may be disordered by vestibular dysfunction, neurological disorders, problems with the distribution of muscle tone, brain injuries, and other dysfunctions. Growth hormone deficiency (GHD) can lead to many disorders, particularly of the musculoskeletal system. During treatment with recombinant human growth hormone (rhGH), an increase in muscle mass and an improvement in bone structure can be observed in children suffering from hypopituitarism from GHD. METHODS: The study involved 33 children suffering from hypopituitarism with GHD (9 girls and 24 boys), aged 10-14 years old. Measurements of the magnitude of their anterior-posterior spinal curvatures were made using an inclinometer. The children were examined at the medianus of the sacrum bone, the Th12-L1 intervertebral area, and the C7-Th1 intervertebral area. In order to characterize the anterior-posterior curvature of the spine, the results were compared with the general norms reported by Saunders. Statistical calculations were carried out using the statistical package Statistica 10 PL. RESULTS: Lumbar lordosis angles were higher in the patients currently receiving growth hormone (GH) treatment than in those who had yet to receive it. There is a statistically significant positive correlation between the length of growth hormone treatment and the alpha angle. There are also statistically significant correlations between age at the beginning of growth hormone therapy and the angle of lordosis. Statistically significant correlations were also seen between age at the beginning of growth hormone therapy and the alpha angle. CONCLUSIONS: Although there may be changes in posture at the beginning of rhGH treatment, the sooner growth hormone therapy begins, the better the body posture. The longer the growth hormone treatment, the better the posture, as expressed by the alpha angle in the sagittal plane.


Assuntos
Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Hipopituitarismo/complicações , Curvaturas da Coluna Vertebral/fisiopatologia , Adolescente , Fatores Etários , Criança , Feminino , Humanos , Hipopituitarismo/fisiopatologia , Lordose/etiologia , Lordose/fisiopatologia , Vértebras Lombares/fisiopatologia , Masculino , Postura , Curvaturas da Coluna Vertebral/etiologia , Fatores de Tempo
11.
Rev. chil. pediatr ; 90(6): 598-605, dic. 2019. tab
Artigo em Espanhol | LILACS | ID: biblio-1058190

RESUMO

INTRODUCCIÓN: La radioterapia, quimioterapia y la cirugía empleada en el tratamiento de los tumores cerebrales tienen efectos en el eje hipotálamo-hipofisario y pueden resultar en disfunción endocrina hasta en el 96% de los casos. PACIENTES Y MÉTODO: Estudio retrospectivo y descriptivo en pacientes diagnos ticados de meduloblastoma sometidos a tratamiento con quimio y radioterapia en los últimos 20 años en un hospital terciario. Se analizan variables edad, sexo, peso, talla, índice de masa corporal (IMC) al final del seguimiento, estadio de maduración sexual, niveles séricos de TSH y T4 libre, ACTH/cortisol e IGF-1, FSH, LH, estradiol, testosterona, perfil lipídico (colesterol total) y prueba de función dinámica de hormona de crecimiento. RESULTADOS: Muestra total de 23 pacientes. El déficit de hormona de crecimiento es la secuela más frecuente (82 %) seguido de disfunción ti roidea (44,8%) y disfunción puberal (24,1%). Solo se diagnosticó un caso de diabetes insípida y 2 casos de déficit de corticotrofina. CONCLUSIONES: El seguimiento a largo plazo de los supervivientes de meduloblastoma tratados con quimio y radioterapia revela una prevalencia muy alta de disfun ción endocrina, particularmente de deficiencia de hormona del crecimiento y de hipotiroidismo. Creemos oportuna la monitorización y el seguimiento a largo plazo de estos pacientes con el fin de garantizar un manejo terapéutico adecuado de aquellas disfunciones tratables.


INTRODUCTION: Radiation therapy, chemotherapy, and surgery used to treat brain tumors have effects on the hy pothalamic-pituitary-adrenal axis and can result in endocrine dysfunction in up to 96% of cases. PATIENTS Y METHOD: Retrospective and descriptive study in patients diagnosed with medulloblasto ma who underwent treatment with chemo and radiotherapy in the last 20 years in a tertiary hospital. The variables analyzed were age, sex, weight, height, body mass index (BMI) at the end of follow-up, sexual maturity stage, serum levels of TSH and free T4, ACTH/cortisol and IGF-1, FSH, LH, estradiol, testosterone, lipid profile (total cholesterol), and growth hormone dynamic function test. RESULTS: Total sample of 23 patients. Growth hormone deficiency is the most frequent sequelae (82%) fo llowed by thyroid dysfunction (44.8%), and disorders of puberty (24.1%). Only one case of diabetes insipidus and two cases of corticotropin deficiency were diagnosed. CONCLUSIONS: Long-term follow- up of medulloblastoma survivors treated with chemo and radiotherapy reveals a very high prevalence of endocrine dysfunction, especially growth hormone deficiency and hypothyroidism. We believe that monitoring and long-term follow-up of these patients is necessary in order to ensure adequate therapeutic management of those treatable dysfunctions.


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Neoplasias Cerebelares/terapia , Quimiorradioterapia/efeitos adversos , Meduloblastoma/terapia , Puberdade Precoce/etiologia , Doenças da Glândula Tireoide/etiologia , Neoplasias Cerebelares/sangue , Estudos Retrospectivos , Hormônio Adrenocorticotrópico/deficiência , Hormônio do Crescimento Humano/deficiência , Diabetes Insípido/etiologia , Doenças do Sistema Endócrino/etiologia , Sobrepeso/etiologia , Sobreviventes de Câncer , Hipogonadismo/etiologia , Meduloblastoma/sangue
12.
Metabolism ; 101: 153998, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31666193

RESUMO

BACKGROUND: The incidence of growth hormone deficiency (GHD) in adamantinomatous craniopharyngioma (aCP) is significantly higher than in other sellar region tumors, but the possible mechanism is still elusive. A high level of inflammatory responses is another feature of aCP. We investigated the internal connection between interleukin-1α (IL-1α) and GHD, while focusing on its biological activities in pituitary fibrosis. MATERIALS AND METHODS: To diagnosis of GHD, the Body Mass Index (BMI), Insulin Like Growth Factor-1(IGF-1) and peak growth hormone (GH) values after insulin stimulation test of 15 aCP patients were recorded. Histological staining was performed on the aCP samples. Levels of 9 proinflammatory cytokines in tumor tissue and cell supernatant were detected using Millipore bead arrays. The effect of IL-1α on GH secretion was evaluated in vivo and in vitro. Western blot, qRT-PCR and cell functional assays were used to explore the potential mechanism through which IL-1α acts on GH secretion. The stereotactic ALZET osmotic pump technique was used to simulate aCP secretion of proinflammatory cytokines in rats. Recombinant IL-1α (rrIL-1α) and conditioned media (CM) prepared from the supernatant of aCP cells was infused directly into the intra-sellar at a rate of 1 µl/h over 28 days, and then the effects of IL-1α treatment on pathological changes of pituitary gland and GH secretion were measured. To further confirm whether IL-1α affects GH secretion through IL-1R1, an IL-1R1 blocker (IL-1R1a, 10 mg/kg body weight, once daily) was administered subcutaneously from the first day until day 28. RESULTS: There was a significant positive correlation between pituitary fibrosis and GHD (rS = 0.756, P = 0.001). A number of cytokines, in particular IL-1α, interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1), were elevated in tumor tissue and cell supernatant. Only IL-1α showed a significant difference between the GHD group and the No-GHD group (P < 0.001, F = 6.251 in tumor tissue; P = 0.003, F = 1.529 in cell supernatant). IL-1α significantly reduced GH secretion in coculture of GH3 and pericytes. The activation of pericytes induced by IL-1α was mediated by the IL-1R1 signaling pathway. In vivo, IL-1α induces pituitary fibrosis, further leading to a decreased level of GH. This pathological change was antagonized by IL-1R1a. CONCLUSION: This study found that the cross talk between aCP cells and stroma cells in the pituitary, i.e. pericytes, is an essential factor in the formation of GHD, and we propose that neutralization of IL-1α signaling might be a potential therapy for GHD in aCP.


Assuntos
Comunicação Celular , Craniofaringioma/patologia , Hormônio do Crescimento Humano/deficiência , Interleucina-1alfa/farmacologia , Pericitos/efeitos dos fármacos , Adulto , Animais , Craniofaringioma/etiologia , Citocinas/metabolismo , Feminino , Fibrose , Hormônio do Crescimento Humano/efeitos dos fármacos , Hormônio do Crescimento Humano/metabolismo , Humanos , Inflamação , Masculino , Pericitos/citologia , Hipófise/metabolismo , Hipófise/patologia , Ratos
13.
Horm Res Paediatr ; 92(3): 150-156, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31707392

RESUMO

INTRODUCTION: Almost 20 years after the first international guidelines on the diagnosis and treatment of GHD have been published, clinical practice varies significantly. The low accuracy of endocrine tests for GHD and the burden caused by ineffective treatment of individual patients were strong motives for national endocrine societies to set up national guidelines regarding how to diagnose GHD in childhood. This audit aims to review the current state and identify common changes, which may improve the diagnostic procedure. METHODS: A group of eight German pediatric endocrinologists contacted eight pediatric endocrinologists from Spain, France, Poland, the UK, the Netherlands, Denmark, Italy, and the US. Each colleague responded as a representative for the own country to a detailed questionnaire containing 22 open questions about national rules, guidelines, and practice with respect to GHD diagnostics and GH prescription. The results were presented and discussed in a workshop and then documented in this study which was reviewed by all participants. RESULTS: National guidelines are available in 7 of 9 countries. GH is prescribed by pediatric endocrinologists in most countries. Some countries have established boards that review and monitor prescriptions. Preferred GH stimulation tests and chosen cutoffs vary substantially. Overall, a trend to lowering the GH cutoff was identified. Priming is becoming more popular and now recommended in 5 out of 9 countries; however, with different protocols. The definition of pretest-conditions that qualify the patient to undergo GH testing varies substantially in content and strictness. The most frequently used clinical sign is low height velocity, but definition varies. Height, IGF-1, and bone age are additional parameters recommended in some countries. CONCLUSIONS: GHD diagnostics varies substantially in eight European countries and in the US. It seems appropriate to undertake further efforts to harmonize endocrine diagnostics in Europe and the US based on available scientific evidence.


Assuntos
Técnicas de Diagnóstico Endócrino/normas , Hormônio do Crescimento Humano/deficiência , Guias de Prática Clínica como Assunto/normas , Dinamarca , Europa (Continente) , Feminino , França , Alemanha , Hormônios Esteroides Gonadais/administração & dosagem , Hormônio do Crescimento Humano/sangue , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Lactente , Cooperação Internacional , Itália , Masculino , Países Baixos , Polônia , Valores de Referência , Espanha , Inquéritos e Questionários , Reino Unido , Estados Unidos
14.
Sci Rep ; 9(1): 16181, 2019 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-31700044

RESUMO

This study investigated the relationship between peak stimulated growth hormone (GH) and body mass index (BMI), as well as the impact of BMI on therapeutic response in patients with GH deficiency (GHD). A total of 460 patients were enrolled in the study. The patients were divided into four groups as per the etiology and peak GH values: idiopathic (n = 439), organic (n = 21), complete (n = 114), and partial (n = 325) GHD groups. Subsequently, they were classified as normal, overweight, or obese based on their BMI. There was no difference in BMI between complete and partial GHD. A significant negative relationship between peak GH and BMI were found. Moreover, obese GHD children had a considerably better therapeutic response in height increase and BMI decrease during 2 years of GH treatment compared to non-obese children with GHD. There was no difference between peak GH and type of GH stimulation test (GHST), except the clonidine test, which showed a much lower peak GH in obese GHD children. In conclusion, BMI had a negative impact on peak GH response, and therapeutic outcome was more favorable in the obese group. Despite no difference in GH response by type of GHST, the degree of obesity differentially affected the results.


Assuntos
Índice de Massa Corporal , Transtornos do Crescimento , Hormônio do Crescimento Humano , Obesidade Pediátrica , Criança , Feminino , Transtornos do Crescimento/tratamento farmacológico , Transtornos do Crescimento/patologia , Transtornos do Crescimento/fisiopatologia , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/deficiência , Humanos , Masculino , Obesidade Pediátrica/tratamento farmacológico , Obesidade Pediátrica/patologia , Obesidade Pediátrica/fisiopatologia
15.
Expert Rev Endocrinol Metab ; 14(6): 419-436, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31721610

RESUMO

Introduction: There have been significant clinical advances in the understanding of the diagnosis and benefits of long-term recombinant human growth hormone (rhGH) replacement in adults with GH deficiency (GHD) since its approval in 1996 by the United States Food and Drug Administration.Areas covered: We searched PubMed, Medline, CINAHL, EMBASE and PsychInfo databases between January 2000 and June 2019 for published studies evaluating adults with GHD. We reviewed the data of the oral macimorelin test compared to the GHRH plus arginine and the insulin tolerance tests that led to its approval by the United States FDA and European Medicines Agency for adult diagnostic testing. We summarize the clinical advances of long-term benefits of rhGH therapy and the potential effects of GH receptor polymorphisms on individual treatment responsiveness. We identify that non-adherence and discontinuation rates are high and recommend strategies to support patients to improve adherence. We also provide an overview of several long-acting GH (LAGH) preparations currently under development and their potential role in improving treatment adherence.Expert opinion: This article summarizes recent clinical advances in rhGH replacement therapy, the biological and molecular aspects that may influence rhGH action, and offers practical strategies to enhance adherence in adults with GHD.


Assuntos
Nanismo Hipofisário/tratamento farmacológico , Terapia de Reposição Hormonal/métodos , Hormônio do Crescimento Humano/deficiência , Adesão à Medicação , Adulto , Nanismo Hipofisário/diagnóstico , Nanismo Hipofisário/fisiopatologia , Hormônio Liberador de Hormônio do Crescimento/efeitos adversos , Terapia de Reposição Hormonal/instrumentação , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Arch. endocrinol. metab. (Online) ; 63(6): 608-617, Nov.-Dec. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1055027

RESUMO

ABSTRACT The somatotropic axis is the main hormonal regulator of growth. Growth hormone (GH), also known as somatotropin, and insulin-like growth factor 1 (IGF-1) are the key components of the somatotropic axis. This axis has been studied for a long time and the knowledge of how some molecules could promote or impair hormones production and action has been growing over the last decade. The enhancement of large-scale sequencing techniques has expanded the spectrum of known genes and several other candidate genes that could affect the GH-IGF1-bone pathway. To date, defects in more than forty genes were associated with an impairment of the somatotropic axis. These defects can affect from the secretion of GH to the bioavailability and action of IGF-1. Affected patients present a large heterogeneous group of conditions associated with growth retardation. In this review, we focus on the description of the GH-IGF axis genetic defects reported in the last decade. Arch Endocrinol Metab. 2019;63(6):608-17


Assuntos
Humanos , Fator de Crescimento Insulin-Like I/genética , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/genética , Transtornos do Crescimento/genética , Mutação/genética , Fenótipo , Fator de Crescimento Insulin-Like I/metabolismo , Transdução de Sinais , Genótipo , Transtornos do Crescimento/metabolismo
17.
Arch. endocrinol. metab. (Online) ; 63(6): 582-591, Nov.-Dec. 2019. tab
Artigo em Inglês | LILACS | ID: biblio-1055018

RESUMO

ABSTRACT GH is one of the insulin counterregulatory hormones which acts in the opposite way to insulin, increasing the glucose production by the liver and kidneys and decreasing glucose uptake from peripheral tissues, thus being a hyperglycemic hormone. When in excess, as in acromegaly, it induces glucose intolerance and diabetes. As expected, patients with GH deficiency (GHD) have hypoglycemia, especially in early childhood, but as GH is also a lipolytic hormone, these patients are becoming obese with higher percentages of body fat. Although obesity in general is directly related to insulin resistance, in patients with GH secretion disorders this relationship may be altered. In acromegaly there is a decrease in fat mass with worsening insulin sensitivity and mice with isolated GHD are characterized by greater insulin sensitivity despite excess fat mass. In humans with GHD, body composition shows increased body fat and decreased free fat mass, but the results regarding insulin sensitivity are still controversial in these patients. These discrepant results regarding insulin sensitivity in patients with GHD suggest the existence of other variables influencing these results. In the present review, we will try to follow the path of the different researches conducted on this subject, both in animal and human models, with the goal of understanding the current knowledge of insulin sensitivity across the spectrum of GHD. Arch Endocrinol Metab. 2019;63(6):582-91


Assuntos
Humanos , Animais , Resistência à Insulina/fisiologia , Transdução de Sinais/fisiologia , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/fisiologia , Glucose/fisiologia , Glucose/metabolismo
18.
Arch. endocrinol. metab. (Online) ; 63(6): 592-600, Nov.-Dec. 2019. tab
Artigo em Inglês | LILACS | ID: biblio-1055015

RESUMO

ABSTRACT Growth hormone (GH) deficiency (GHD) in adults is well-characterized and includes abnormal body composition, reduced bone mass, an adverse cardiovascular risk profile, and impaired quality of life. In the early 1990s, it was also shown that patients with hypopituitarism without GH replacement therapy (GHRT) had excess mortality. Today, GHRT has been shown to decrease or reverse the negative effects of GHD. In addition, recent papers have shown that mortality and morbidity are approaching normal in hypopituitary patients with GHD who receive modern endocrine therapy including GHRT. Since the first dose-finding studies, it has been clear that efficacy and side effects differ substantially between patients. Many factors have been suggested as affecting responsiveness, such as sex, age, age at GHD onset, adherence, and GH receptor polymorphisms, with sex and sex steroid replacement having the greatest impact. Therefore, the individual tailoring of GH dose is of great importance to achieve sufficient efficacy without side effects. One group that stands out is women receiving oral estrogen replacement, who needs the highest dose. Serum insulin-like growth factor-1 (IGF-1) is still the most used biochemical biomarker for GH dose titration, although the best serum IGF-1 target is still debated. Patients with GHD due to acromegaly, Cushing's disease, or craniopharyngioma experience similar effects from GHRT as others. Arch Endocrinol Metab. 2019;63(6):592-600


Assuntos
Humanos , Masculino , Feminino , Adulto , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/deficiência , Terapia de Reposição Hormonal/métodos , Adesão à Medicação , Medicina de Precisão , Qualidade de Vida , Idade de Início
19.
Ital J Pediatr ; 45(1): 130, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31639023

RESUMO

Recombinant human growth hormone (rhGH) is an approved and effective treatment for short children born small for gestational age (SGA). Prevalence of children eligible for treatment as SGA is reported to be 1:1800. The latest data from the National Registry of Growth Hormone therapy (RNAOC) showed that the number of children treated with SGA indication is still small (prevalence 0.37/100,000) and these children are significantly less reported than those treated for growth hormone deficiency (GHD), although GHD prevalence is 1:4000-1:10,000. This means that many short children born SGA are still not properly identified, and therefore not treated with rhGH, or misdiagnosed as GHD. This article provides some practical tools for the identification of children eligible for rhGH treatment.


Assuntos
Estatura , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Recém-Nascido Pequeno para a Idade Gestacional , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Itália , Masculino , Guias de Prática Clínica como Assunto
20.
Growth Factors ; 37(3-4): 170-177, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31576764

RESUMO

Lowe syndrome is an x-linked disorder characterized by congenital cataracts, nervous system abnormalities and renal tubular dysfunction. With the rising number of reported cases, more patients are found to suffer from endocrine abnormalities. Hereby, three Chinese patients with typical symptoms and extremely short stature were described. The OCRL gene was analyzed. A combination of blood biochemistry and radiological examinations were performed. Growth hormone provocation test was taken in one patient. Nucleotide sequence analysis revealed a de novo novel hemizygous mutation (c.2290_2291delinsCT) in exon 21 in an adolescent boy. As indicated by the growth hormone provocation test, the boy had growth hormone deficiency. The other two patients were brothers with extremely short stature, and manifested the same hemizygous mutation (c.2581G > A) in exon 23. It was speculated that the mutation of OCRL gene could lead to deficiency of growth hormone, for which an early growth hormone intervention may be beneficial.


Assuntos
Desenvolvimento Infantil/fisiologia , Hormônio do Crescimento Humano/deficiência , Síndrome Oculocerebrorrenal/genética , Monoéster Fosfórico Hidrolases/genética , Adolescente , Sequência de Bases , Estatura/genética , Criança , Pré-Escolar , China , Humanos , Masculino , Mutação/genética , Síndrome Oculocerebrorrenal/patologia , Análise de Sequência de DNA
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