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1.
Front Endocrinol (Lausanne) ; 15: 1345363, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481440

RESUMO

X-linked acrogigantism (X-LAG) is a rare form of pituitary gigantism that is associated with growth hormone (GH) and prolactin-secreting pituitary adenomas/pituitary neuroendocrine tumors (PitNETs) that develop in infancy. It is caused by a duplication on chromosome Xq26.3 that leads to the misexpression of the gene GPR101, a constitutively active stimulator of pituitary GH and prolactin secretion. GPR101 normally exists within its own topologically associating domain (TAD) and is insulated from surrounding regulatory elements. X-LAG is a TADopathy in which the duplication disrupts a conserved TAD border, leading to a neo-TAD in which ectopic enhancers drive GPR101 over-expression, thus causing gigantism. Here we trace the full diagnostic and therapeutic pathway of a female patient with X-LAG from 4C-seq studies demonstrating the neo-TAD through medical and surgical interventions and detailed tumor histopathology. The complex nature of treating young children with X-LAG is illustrated, including the achievement of hormonal control using a combination of neurosurgery and adult doses of first-generation somatostatin analogs.


Assuntos
Acromegalia , Doenças Genéticas Ligadas ao Cromossomo X , Gigantismo , Hormônio do Crescimento Humano , Neoplasias Hipofisárias , Adulto , Humanos , Criança , Feminino , Pré-Escolar , Gigantismo/genética , Gigantismo/terapia , Gigantismo/metabolismo , Acromegalia/patologia , Hormônio do Crescimento/metabolismo , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia
2.
Front Endocrinol (Lausanne) ; 15: 1348972, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38449845

RESUMO

Introduction: The mortality ratio in patients with acromegaly has improved over the last few decades. We aimed to determine the mortality rate and correlated factors in patients with acromegaly before and after the introduction of national protocols for treatment. In addition, we determined whether there are sex-related differences in mortality of patients with acromegaly. Methods: This observational retrospective study included 399 consecutive patients with acromegaly between January 2001-December 2022. Paraclinical data included random growth hormone (GH) and insulin-like growth factor-I (IGF1) levels, maximal pituitary tumor diameter at diagnosis, first visit, and last evaluation. Standardized mortality ratio (SMR) was calculated by dividing the observed and expected mortality rates. Cox regression analysis revealed the independent factors associated with mortality. Results: At the last visit, 31.07% (124) of patients were cured, 22.05% (88) had controlled acromegaly with medication, and 45.31% (181) had not controlled acromegaly. During follow-up (13.03 ± 5.65 years, 5216.62 person-years), 89 patients died (0.017%), resulting in an SMR of 1.18 [95% CI 0.95-1.45]. The independent factors associated with mortality were the last IGF1 level/last random GH level, absence of surgery, gonadotropin deficiency, and age. Patients with normal IGF1 after treatment showed an SMR of 0.71, whereas patients with IGF1 ratio > 1 showed SMR=1.51. Patients diagnosed between 1975-2007 and 2008-2022 had SMR = 1.25 [95% CI 0.97-1.58] and SMR = 1.09 [95% CI 0.68-1.65], respectively. In females with acromegaly, SMR was 1.63 [95% CI 1.24-2.11]; 1.76 [95% CI 1.30-2.34] in women diagnosed before 2008 and 1.33 [95% CI 0.69-2.33] in those diagnosed after 2008. Males with acromegaly had a mortality ratio similar to males from the general population (SMR = 0.99, [95% CI 0.66-1.41]). Conclusion: Patients diagnosed with acromegaly in the last 15 years had lower mortality rates than those diagnosed before 2008, due to the availability of new medications, primarily somatostatin receptor analogs and to a higher proportion of patients undergoing surgery. Females still have a high mortality ratio owing to older age at diagnosis and higher risk of metabolic complications. Therefore, efforts should be made for early diagnosis of acromegaly in women.


Assuntos
Acromegalia , Hormônio do Crescimento Humano , Hipopituitarismo , Masculino , Humanos , Feminino , Estudos Retrospectivos , Hormônio do Crescimento
3.
Front Endocrinol (Lausanne) ; 15: 1288497, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495788

RESUMO

Introduction: It has been proposed that not all children with short stature displaying an inadequate response to tests for growth hormone (GH) secretion truly suffer from GH deficiency (GHD). Only children with a monogenic cause of GHD or an identifiable combined hormonal deficiency or anatomical anomaly in the hypothalamic-pituitary axis should be considered definite GHD (dGHD). The remaining patients can be defined as a separate group of patients, "short stature unresponsive to stimulation tests" (SUS). The aim of this proof-of-concept study, was to assess whether SUS patients treated with rhGH exhibit any differences compared to GHD patients undergoing the same treatment. Methods: Retrospective analysis on 153 consecutive patients with short stature and pathological response to two GH stimulation tests. Patients with dGHD were defined as those with a clear genetic or anatomical hypothalamic-pituitary anomaly, as well as those with combined pituitary hormone deficiencies and those with a known insult to the hypothalamic-pituitary axis (i.e. total brain irradiation) (n=38, 25%); those without any of the previous anomalies were defined as SUS (n=115, 75%). Results: At diagnosis, dGHD and SUS populations did not differ significantly in sex (F 32% vs 28%, p=0.68), age (11.9 vs 12.1, p=0.45), height SDS at diagnosis (-2.2 vs. -2.0, p=0.35) and prevalence of short stature (height <-2 SDS) (56% vs 51%, p=0.45). IGF-1 SDS were significantly lower in dGHD (-2.0 vs -1.3, p<0.01). After 1 year of treatment, the prevalence of short stature was significantly reduced in both groups (31% in dGHD vs. 21% in SUS, p<0.01) without any significant differences between groups (p=0.19), while the increase in IGF-1 SDS for bone age was greater in the dGHD category (+1.9 vs. +1.5, p<0.01), with no further difference in IGF-1 SDS between groups. At the last available follow-up, 59 patients had reached the near adult height (NAH) and underwent retesting for GHD. No differences in NAH were found (-0.3 vs. -0.4 SDS, 0% vs. 4% of short stature). The prevalence of pathological retesting was higher in dGHD (60% vs. 10%, p<0.01) as well as of overweight and obesity (67% vs. 26%). Conclusion: Stimulation tests and the equivalent benefit from rhGH therapy, cannot distinguish between dGHD and SUS populations. In addition, lower IGF-1 concentrations at baseline and their higher increase during treatment in dGHD patients, and the lack of pathological retesting upon reaching NAH in SUS patients, are facts that suggest that deficient GH secretion may not be the cause of short stature in the SUS studied population.


Assuntos
Nanismo Hipofisário , Hormônio do Crescimento Humano , Criança , Adulto , Humanos , Fator de Crescimento Insulin-Like I , Estudos Retrospectivos , Nanismo Hipofisário/diagnóstico , Nanismo Hipofisário/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Hormônio do Crescimento
4.
Front Endocrinol (Lausanne) ; 15: 1360139, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505755

RESUMO

Background: Increased risk of neoplastic events after recombinant human growth hormone (rhGH) treatment in childhood has been an ongoing concern but long-term safety data are limited. Methods: A nationwide population-based cohort study in Sweden of patients treated with rhGH during childhood between 1985-2010, due to isolated growth hormone deficiency (GHD), small for gestational age (SGA) and idiopathic short stature (ISS). The comparison group consisted of 15 age-, sex-, and region-matched controls per patient, randomly selected from the general population. Data on neoplastic events and covariates, such as gestational age, birth weight, birth length, socioeconomic status, and height at study start, were collected through linkage with population-based registers. The cohort was followed for neoplastic events until the end of 2020. Results: 53,444 individuals (3,408 patients; 50,036 controls) were followed for up to 35 years, with a median follow-up of 19.8 years and a total of 1,050,977 person-years. Patients showed a moderately increased hazard ratio (HR) for neoplastic events overall compared to controls (HR 1.28, 95% CI: 1.12-1.46), but only significant for males (HR 1.39, 95% CI: 1.17-1.66) and not females (HR 1.15, 95% CI: 0.94-1.41). Longer treatment duration was associated with an increased HR, but no association was found between neoplastic events and mean or cumulative dose. No increased risk of malignant neoplasms was observed for the patients compared to matched controls (HR 0.91 95% CI: 0.66-1.26). Conclusion: No association was found between rhGH treatment during childhood for GHD, SGA, or ISS and malignant neoplastic events in early to mid-adulthood. A moderate increase in overall neoplastic events was observed due to an increased number of events in male patients.


Assuntos
Nanismo Hipofisário , Hormônio do Crescimento Humano , Neoplasias , Humanos , Masculino , Adulto , Hormônio do Crescimento , Suécia/epidemiologia , Estudos de Coortes , Peso ao Nascer , Nanismo Hipofisário/tratamento farmacológico , Proteínas Recombinantes/uso terapêutico , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia
5.
Probl Endokrinol (Mosk) ; 70(1): 4-12, 2024 Feb 27.
Artigo em Russo | MEDLINE | ID: mdl-38433536

RESUMO

The recombinant technologies era, which began in the second half of the XX century, made it possible to produce recombinant growth hormone (rGH) necessary for the treatment of stunting of various genesis. The time of practically unlimited possibilities of rGH production has come, which served as a stimulus for studying the efficacy and safety of rGH application, searching for optimal ways of its use and dosing regimes. Many years of experience in the use of somatropin in clinical practice allowed us to obtain data on its effectiveness primarily in somatotropic insufficiency in children, to study its effect on the functional state of various organs and systems, and to expand the indications for the use of RGR.


Assuntos
Hormônio do Crescimento , Hormônio do Crescimento Humano , Criança , Humanos , Hormônio do Crescimento/uso terapêutico , Hormônio do Crescimento Humano/efeitos adversos , Transtornos do Crescimento/tratamento farmacológico , Tecnologia , Triancinolona
6.
Probl Endokrinol (Mosk) ; 70(1): 66-80, 2024 Feb 14.
Artigo em Russo | MEDLINE | ID: mdl-38433543

RESUMO

 Acromegaly is a neuroendocrine disorder caused by excessive production of growth hormone (GH). In the majority of cases the cause of acromegaly is a pituitary tumor producing GH. Cases of ectopic acromegaly are much rarer. Ectopic acromegaly occurs in cases of tumors which produce growth hormone-releasing hormone (GHRH) or extrapituitary tumors which produce GH. The main sources of excessive GHRH production are neuroendocrine tumors (NETs) of the lung or pancreas. Treatment of ectopic acromegaly consists of surgical removal of the source of GHRH hyperproduction and in cases where surgery is not an option, somatostatin analogues, pegvisomant, chemotherapy, immunotherapy or radiation therapy are used.In this article three cases of ectopic acromegaly due to GHRH-producing lung NETs are presented, each of them being notable for a number of features. In the first two cases, clinical symptoms were mild, besides in the second case ectopic acromegaly was accompanied by primary hyperparathyroidism. In the third case ectopic acromegaly was accompanied by pituitary macroadenoma, and after surgical removal of the lung NET remission of acromegaly was not achieved. In all three cases, lung NETs were detected incidentally on radiologic chest screening for other conditions.


Assuntos
Acromegalia , Carcinoma Neuroendócrino , Neoplasias Pulmonares , Tumores Neuroendócrinos , Humanos , Acromegalia/complicações , Acromegalia/cirurgia , Tumores Neuroendócrinos/complicações , Tumores Neuroendócrinos/terapia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/cirurgia , Hormônio do Crescimento , Federação Russa
7.
Drug Des Devel Ther ; 18: 667-684, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38454934

RESUMO

Purpose: Omnitrope® (somatropin) was approved as a biosimilar recombinant human growth hormone (rhGH) in 2006. Here, we report final data from the PAtients TReated with Omnitrope® (PATRO) Children study, a post-marketing surveillance study designed to monitor the long-term safety and effectiveness of this treatment in pediatric patients. Methods: The study population included all pediatric patients treated with Omnitrope® (biosimilar rhGH), administered via daily injection, in routine clinical practice. The primary objective was to assess long-term safety, with effectiveness assessed as a secondary objective. Results: In total, 7359 patients were enrolled and treated in the PATRO Children study; 86.0% were treatment-naïve at baseline. Growth hormone deficiency was the most frequent indication (57.9%), followed by patients born small for gestational age (SGA; 26.6%). The mean (SD) duration of exposure to biosimilar rhGH was 3.66 years (2.39). A total of 16,628 adverse events (AEs) were reported in 3981 (54.1%) patients, most of which were mild/moderate. AEs suspected to be treatment related occurred in 8.3% of patients, most frequently headache (1.6%), injection-site pain (1.1%), or injection-site hematoma (1.1%). The incidence rate (IR) of type 2 diabetes mellitus was 0.11 per 1000 person-years (PY) across all patients, and 0.13 per 1000 PY in patients born SGA. The IR of newly diagnosed primary malignancies was 0.22 per 1000 PY across all patients. In the 6589 patients included in the effectiveness population, a sustained catch-up growth was observed across all indications. After 5 years of treatment, height SDS increased from baseline by a median (range) of +1.79 (-3.7 to 6.2) in treatment-naïve patients and +0.73 (-1.4 to 3.7) in pretreated patients. Conclusion: This final analysis of the PATRO Children study indicates that biosimilar rhGH is well tolerated and effective in real-world clinical practice. These data are consistent with the well-characterized safety profile of rhGH treatment in pediatric patients.


Assuntos
Medicamentos Biossimilares , Diabetes Mellitus Tipo 2 , Hormônio do Crescimento Humano , Humanos , Criança , Hormônio do Crescimento Humano/efeitos adversos , Hormônio do Crescimento , Medicamentos Biossimilares/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Proteínas Recombinantes/efeitos adversos , Vigilância de Produtos Comercializados
8.
J Integr Neurosci ; 23(2): 32, 2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38419439

RESUMO

The role of growth hormone (GH) in the central nervous system (CNS) involves neuroprotection, neuroregeneration, formation of axonal projections, control of cognition, and regulation of metabolism. As GH induces insulin-like growth factor-1 (IGF-1) expression in many tissues, differentiating the specific functions of GH and IGF-1 in the organism is a significant challenge. The actions of GH and IGF-1 in neurons have been more extensively studied than their functions in nonneuronal cells (e.g., microglial cells). Glial cells are fundamentally important to CNS function. Microglia, astrocytes, oligodendrocytes, and tanycytes are essential to the survival, differentiation, and proliferation of neurons. As the interaction of the GH/IGF-1 axis with glial cells merits further exploration, our objective for this review was to summarize and discuss the available literature regarding the genuine effects of GH on glial cells, seeking to differentiate them from the role played by IGF-1 action whenever possible.


Assuntos
Hormônio do Crescimento , Fator de Crescimento Insulin-Like I , Hormônio do Crescimento/farmacologia , Hormônio do Crescimento/fisiologia , Microglia/metabolismo , Astrócitos/metabolismo , Sistema Nervoso Central/metabolismo
9.
JAMA Netw Open ; 7(2): e240447, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38421647

RESUMO

Importance: Youth-onset type 2 diabetes (T2D) has a more aggressive phenotype than adult-onset T2D, including rapid loss of glycemic control and increased complication risk. Objective: To identify associations of growth hormone mediators with glycemic failure, beta cell function, and insulin sensitivity in youth-onset T2D. Design, Setting, and Participants: This post hoc secondary analysis of the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) randomized clinical trial, which enrolled participants from July 2004 to February 2009, included 398 participants from 15 university-affiliated medical centers with available plasma samples from baseline and 36 months. Participants were youths aged 10 to 17 years with a duration of T2D of less than 2 years who were randomized to metformin, metformin plus lifestyle intervention, or metformin plus rosiglitazone. Participants were followed up for a mean (SD) of 3.9 (1.5) years during the trial, ending in 2011. Statistical analysis was performed from August 2022 to November 2023. Exposure: Plasma insulin-like growth factor-1 (IGF-1), growth hormone receptor (GHR), and insulin-like growth factor binding protein 1 (IGFBP-1). Main Outcomes and Measures: Main outcomes were (1) loss of glycemic control during the TODAY study, defined as hemoglobin A1c (HbA1c) level of 8% or more for 6 months or inability to wean from insulin therapy, and (2) baseline and 36-month measures of glycemia (fasting glucose, HbA1c), insulin sensitivity (1/fasting C-peptide), high-molecular-weight adiponectin, and beta cell function (C-peptide index, C-peptide oral disposition index). Results: This analysis included 398 participants (mean [SD] age, 13.9 [2.0] years; 248 girls [62%]; 166 Hispanic participants [42%]; 134 non-Hispanic Black participants [34%], and 84 non-Hispanic White participants [21%]). A greater increase in IGF-1 level between baseline and 36 months was associated with lower odds of glycemic failure (odds ratio [OR], 0.995 [95% CI, 0.991-0.997]; P < .001) and higher C-peptide index per 100-ng/mL increase in IGF-1 (ß [SE], 0.015 [0.003]; P < .001). A greater increase in log2 GHR level between baseline and 36 months was associated with higher odds of glycemic failure (OR, 1.75 [95% CI, 1.05-2.99]; P = .04) and lower C-peptide index (ß [SE], -0.02 [0.006]; P < .001). A greater increase in log2 IGFBP-1 level between baseline and 36 months was associated with higher odds of glycemic failure (OR, 1.37 [95% CI, 1.09-1.74]; P = .007) and higher high-molecular-weight adiponectin (ß [SE], 431 [156]; P = .007). Conclusions and Relevance: This study suggests that changes in plasma growth hormone mediators are associated with loss of glycemic control in youth-onset T2D, with IGF-1 associated with lower risk and GHR and IGFBP-1 associated with increased risk. Trial Registration: ClinicalTrials.gov Identifier: NCT00081328.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Metformina , Adulto , Feminino , Adolescente , Humanos , Hormônio do Crescimento , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina , Fator de Crescimento Insulin-Like I , Diabetes Mellitus Tipo 2/tratamento farmacológico , Controle Glicêmico , Adiponectina , Peptídeo C , Hemoglobinas Glicadas , Metformina/uso terapêutico
10.
Environ Sci Pollut Res Int ; 31(10): 15821-15836, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38305968

RESUMO

The current investigation explores the mechanisms of ammonia and arsenic toxicity, along with high-temperature stress, which other researchers rarely addressed. Pangasianodon hypophthalmus was exposed to low doses of ammonia and arsenic (1/10th of LC50, 2.0 and 2.68 mg L-1, respectively) and high temperature (34 °C) for 105 days. The following treatments were applied: control (unexposed), arsenic (As), ammonia (NH3), ammonia + arsenic (NH3 + As), ammonia + temperature (NH3 + T), and NH3 + As + T. Cortisol levels significantly increased with exposure to ammonia (NH3), arsenic (As), and high temperature (34 °C) compared to the unexposed group. Heat shock protein (HSP 70), inducible nitric oxide synthase (iNOS), and metallothionein (MT) gene expressions were notably upregulated by 122-210%, 98-122%, and 64-238%, respectively, compared to the control. Neurotransmitter enzymes (acetylcholine esterase, AChE) were significantly inhibited by NH3 + As + T, followed by other stressor groups. The apoptotic (caspase, Cas 3a and 3b) and detoxifying (cytochrome P450, CYP P450) pathways were substantially affected by the NH3 + As + T group. Immune (total immunoglobulin, Ig; tumor necrosis factor TNFα; and interleukin IL) and growth-related genes (growth hormone, GH; growth hormone regulator, GHR1 and GHRß; myostatin, MYST and somatostatin, SMT) were noticeably upregulated by NH3 + As + T, followed by other stress groups, compared to the control group. Weight gain %, protein efficiency ratio, feed efficiency ratio, specific growth rate, and other growth attributes were significantly affected by low doses of ammonia, arsenic, and high-temperature stress. Albumin, total protein, globulin, A:G ratio, and myeloperoxidase (MPO) were highly affected by the As + NH3 + T group. Blood profiling, including red blood cells (RBC), white blood count (WBC), and hemoglobin (Hb), were also impacted by stressor groups compared to the control group. Genotoxicity, as DNA damage, was significantly higher in groups exposed to NH3 + As + T (89%), NH3 + T (78%), NH3 (73), NH3 + As (71), and As (68%). The bioaccumulation of arsenic was substantially higher in liver and kidney tissues. The present study contributes to understanding the toxicity mechanisms of ammonia and arsenic, as well as high-temperature stress, through different gene expressions, biochemical attributes, genotoxicity, immunological status, and growth performance of P. hypophthalmus.


Assuntos
Arsênio , Arsênio/toxicidade , Amônia , Temperatura , Antioxidantes/metabolismo , Hormônio do Crescimento
11.
Zhonghua Yi Xue Za Zhi ; 104(6): 450-452, 2024 Feb 06.
Artigo em Chinês | MEDLINE | ID: mdl-38326058

RESUMO

To analyze the clinical features of patients with anterior hypopituitarism (HP) complicated with cirrhosis, and to explore the effects of growth hormone supplementation on liver and lung function. A total of 11 patients with HP complicated with cirrhosis admitted to Peking Union Medical College Hospital from January 2016 to December 2022 were included in the study, including 8 males and 3 females, aged [M(Q1, Q3)]31 (20, 37) years. There were 6 patients with pituitary stalk interruption syndrome, 4 patients after craniopharyngioma resection, and 1 patient after germinal cell tumor chemoradiotherapy. Cirrhosis appeared at [M(Q1, Q3)]7 (1, 16) years after the diagnosis of HP. There were 7 cases complicated with hepatopulmonary syndrome (HPS). The liver and lung function of 5 patients were improved significantly after the addition of growth hormone, and the arterial partial pressure of oxygen increased from (47±11) mmHg(1 mmHg=0.133 kPa) to (84±12) mmHg. Timely supplementation of growth hormone can improve the symptoms of fatty liver, cirrhosis and HPS, and postpone or even avoid the transplantation of liver and other organs.


Assuntos
Síndrome Hepatopulmonar , Hormônio do Crescimento Humano , Hipopituitarismo , Neoplasias Hipofisárias , Humanos , Masculino , Feminino , Idoso , Hormônio do Crescimento , Cirrose Hepática , Hipopituitarismo/complicações , Hipopituitarismo/patologia , Síndrome Hepatopulmonar/complicações , Síndrome Hepatopulmonar/diagnóstico , Pulmão/patologia , Suplementos Nutricionais
12.
J Feline Med Surg ; 26(2): 1098612X241226690, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38323402

RESUMO

PRACTICAL RELEVANCE: Diabetes mellitus is the second-most common feline endocrinopathy, affecting an estimated 1/200 cats. While the underlying causes vary, around 15-25% of cats with diabetes mellitus develop the condition secondarily to progressive growth hormone (GH)-induced insulin resistance. This typically results in a form of diabetes that is challenging to manage, whereby the response to insulin is very variable or high doses are required to achieve even minimal diabetic control. CLINICAL CHALLENGES: Although uncontrolled chronic excessive GH may result in phenotypic changes that raise suspicion for acromegaly, many cats with hypersomatotropism (HST) do not have these changes. In these situations, a clinician's index of suspicion may be increased by the presence of less dramatic changes such as marked polyphagia, stertor or uncontrolled diabetes mellitus. The current diagnostic test of choice is demonstration of a markedly increased serum insulin-like growth factor 1 (IGF1) concentration, but some affected cats will have only a marginal increase; additionally, chronic insulin administration in cats results in an increase in serum IGF1, making the diagnosis less clear cut and requiring additional confirmatory tests. EVIDENCE BASE: Over the past two decades, HST has increasingly been recognised as an underlying cause of diabetes mellitus in cats. This review, which focuses on diagnosis and treatment, utilises data from observational studies, clinical trials and case series, as well as drawing on the experience of the authors in managing this condition.


Assuntos
Acromegalia , Doenças do Gato , Diabetes Mellitus , Gatos , Animais , Acromegalia/veterinária , Hormônio do Crescimento/metabolismo , Hormônio do Crescimento/uso terapêutico , Diabetes Mellitus/veterinária , Insulina/uso terapêutico
13.
Indian Pediatr ; 61(2): 154-157, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38321728

RESUMO

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.


Assuntos
Nanismo Hipofisário , Hormônio do Crescimento Humano , Hipopituitarismo , Criança , Humanos , Masculino , Hormônio do Crescimento/uso terapêutico , Hipófise , Estudos Retrospectivos , Feminino , Lactente , Pré-Escolar , Adolescente
14.
Physiol Plant ; 176(1): e14195, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38332400

RESUMO

This review aims to elucidate the intricate effects and mechanisms of terahertz (THz) wave stress on Pinellia ternata, providing valuable insights into plant responses. The primary objective is to highlight the imperative for future research dedicated to comprehending THz wave impacts across plant structures, with a specific focus on the molecular intricacies governing root system structure and function, from shoots to roots. Notably, this review highlights the accelerated plant growth induced by THz waves, especially in conjunction with other environmental stressors, and the subsequent alterations in cellular homeostasis, resulting in the generation of reactive oxygen species (ROS) and an increase in brassinosteroids. Brassinosteroids are explored for their dual role as toxic by-products of stress metabolism and vital signal transduction molecules in plant responses to abiotic stresses. The paper further investigates the spatio-temporal regulation and long-distance transport of phytohormones, including growth hormone, cytokinin, and abscisic acid (ABA), which significantly influence the growth and development of P. ternata under THz wave stress. With a comprehensive review of Reactive oxygen species (ROS) and Brassinosteroid Insensitive (BRI) homeostasis and signalling under THz wave stress, the article elucidates the current understanding of BRI involvement in stress perception, stress signalling, and domestication response regulation. Additionally, it underscores the importance of spatio-temporal regulation and long-distance transport of key plant hormones, such as growth hormone, cytokinin, and ABA, in determining root growth and development under THz wave stress. The study of how plants perceive and respond to environmental stresses holds fundamental biological significance, and enhancing plant stress tolerance is crucial for promoting sustainable agricultural practices and mitigating the environmental burdens associated with low-tolerance crop cultivation.


Assuntos
Brassinosteroides , Pinellia , Brassinosteroides/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Pinellia/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Ácido Abscísico/metabolismo , Estresse Fisiológico , Citocininas/metabolismo , Plantas/metabolismo , Hormônio do Crescimento/metabolismo , Hormônio do Crescimento/farmacologia
15.
Drug Des Devel Ther ; 18: 291-306, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38333899

RESUMO

Growth hormone (GH) replacement therapy for growth hormone deficiency (GHD) in children and adults has for over 25 years, until recently, been administered as daily injections. This daily treatment regimen often incurs a burden to patients and caregivers, leading to high rates of non-adherence and, consequently, decreased treatment efficacy outcomes. To address this shortcoming, long-acting growth hormones (LAGHs) have been developed with the aim of reducing the burden of daily injections, thereby potentially improving treatment adherence and outcomes. Somapacitan (Sogroya®) (Novo Nordisk, Bagsværd, Denmark) is a LAGH currently approved for the treatment of adult and childhood GHD (AGHD and CGHD, respectively) in several countries. Other LAGHs, such as somatrogon (Ngenla®) (Pfizer, New York, United States) and lonapegsomatropin/TransCon GH (Skytrofa®) (Ascendis Pharma, Copenhagen, Denmark), are also currently approved and available for the treatment of CGHD in several countries. In this review, we will consider the method of protraction, pharmacokinetics (PK) and pharmacodynamics (PD), efficacy, and safety results of somapacitan in adult and pediatric trials and how these characteristics differ from those of the other aforementioned LAGHs. Additionally, the administration of somapacitan and timing of measurement of serum insulin-like growth factor-I (IGF-I) levels are summarized. Information on administration, advice on missed doses, and clinical guidelines are discussed, as well as identifying which patients are suitable for somapacitan therapy, and how to monitor and adjust dosing whilst on therapy.


Assuntos
Nanismo Hipofisário , Histidina , Hormônio do Crescimento Humano , Manitol , Fenol , Adulto , Humanos , Criança , Estados Unidos , Hormônio do Crescimento Humano/uso terapêutico , Nanismo Hipofisário/tratamento farmacológico , Hormônio do Crescimento/farmacocinética , Hormônio do Crescimento/uso terapêutico , Resultado do Tratamento , Fator de Crescimento Insulin-Like I
16.
Clin Endocrinol (Oxf) ; 100(4): 389-398, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38368603

RESUMO

OBJECTIVE: Somapacitan is a long-acting growth hormone (GH) derivative developed for the treatment of GH deficiency (GHD). This study evaluates the efficacy and tolerability of somapacitan in Japanese children with GHD after 104 weeks of treatment and after switch from daily GH. DESIGN: Subanalysis on Japanese patients from a randomised, open-labelled, controlled parallel-group phase 3 trial (REAL4, NCT03811535). PATIENTS AND MEASUREMENTS: Thirty treatment-naïve patients were randomised 2:1 to somapacitan (0.16 mg/kg/week) or daily GH (0.034 mg/kg/day) up to Week 52, after which all patients received somapacitan. Height velocity (HV; cm/year) at Weeks 52 and 104 were the primary measurements. Additional assessments included HV SD score (SDS), height SDS, bone age, insulin-like growth factor-I (IGF-I) SDS, and observer-reported outcomes. RESULTS: At Week 52, observed mean HV was similar between treatment groups (10.3 vs. 9.8 cm/year for somapacitan and daily GH, respectively). Similar HVs between groups were also observed at Week 104: 7.4 cm/year after continuous somapacitan treatment (soma/soma) and 7.9 cm/year after 1-year somapacitan treatment following switch from daily GH (switch). Other height-related endpoints supported continuous growth. IGF-I SDS increased in both groups with mean IGF-I SDS within -2 and +2 during the study. Somapacitan was well tolerated, one mild injection site reaction was reported, with no reports of injection site pain. Patient preference questionnaires showed that most patients and their caregivers (90.9%) who switched treatment at Week 52 preferred once-weekly somapacitan over daily GH treatment. CONCLUSIONS: Somapacitan showed sustained efficacy in Japanese children with GHD over 104 weeks and for 52 weeks after switching from daily GH. Somapacitan was well tolerated and preferred over daily GH.


Assuntos
Nanismo Hipofisário , Histidina , Hormônio do Crescimento Humano , Manitol , Fenol , Criança , Humanos , Hormônio do Crescimento/uso terapêutico , Fator de Crescimento Insulin-Like I , Japão , Nanismo Hipofisário/tratamento farmacológico
17.
Front Endocrinol (Lausanne) ; 15: 1340432, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38318293

RESUMO

Introduction: Hormones play a vital role in development from conception to birth and throughout the human lifespan. These periods are logically divided into fetal development, pre-pubertal growth, puberty, and adulthood. Deviations from standard physiological levels and release patterns of constituent hormones can lead to pathology affecting the normal developmental trajectory. Research is ongoing to better understand the mechanisms of these hormones and how their modulation affects development. Methods: This article focuses on recent developments in understanding the role hormones play in development. We also cover recent discoveries in signaling pathways and hormonal regulation. Results: New and continuing research into functional hormone regulation focuses on sex hormones, gonadotropic hormones, growth hormones, insulin-like growth factor, thyroid hormone, and the interconnectedness of each of these functional axes. Currently, the abundance of work focuses on fertility and correction of sex hormone levels based on an individual's condition and stage in life. Discussion: Continuing research is needed to fully understand the long-term effects of hormone modulation in growth and sexual development. The role of each hormone in parallel endocrine axes should also be more thoroughly investigated to help improve the safety and efficacy in endocrine pharmacotherapeutics.


Assuntos
Hormônios Esteroides Gonadais , Hormônio do Crescimento , Humanos , Hormônios Esteroides Gonadais/fisiologia , Hormônio do Crescimento/fisiologia , Sistema Endócrino , Gonadotropinas , Hormônios Tireóideos
18.
Gene ; 907: 148283, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38354915

RESUMO

BACKGROUND: Isolated growth hormone deficiency (IGHD) is a rare genetically heterogeneous disorder caused primarily by mutations in GH1 and GH releasing hormone receptor (GHRHR). The aim of this study was to identify the molecular etiology of a Chinese boy with IGHD. METHODS: Whole-exome sequencing, sanger sequencing and bioinformatic analysis were performed to screen for candidate mutations. The impacts of candidate mutation on gene expression, intracellular localization and protein function were further evaluated by in vitro assays. RESULTS: A novel heterozygous frameshift mutation in the GHRH gene (c.91dupC, p.R31Pfs*98) was identified in a Chinese boy clinically diagnosed as having IGHD. The mutation was absent in multiple public databases, and considered as deleterious using in silico prediction, conservative analysis and three-dimensional homology modeling. Furthermore, mRNA and protein expression levels of mutant GHRH were significantly increased than wild-type GHRH (p < 0.05). Moreover, mutant GHRH showed an aberrant accumulation within the cytoplasm, and obviously reduced ability to stimulate GH secretion and cAMP accumulation in human GHRHR-expressing pituitary GH3 cells compared to wild-type GHRH (p < 0.05). CONCLUSION: Our study discovered the first loss-of function mutation of GHRH in a Chinese boy with IGHD and provided new insights on IGHD pathogenesis caused by GHRH haploinsufficiency.


Assuntos
Nanismo Hipofisário , Hormônio do Crescimento Humano , Masculino , Humanos , Mutação da Fase de Leitura , Nanismo Hipofisário/genética , Hormônio do Crescimento Humano/genética , Receptores de Neuropeptídeos/genética , Receptores de Hormônios Reguladores de Hormônio Hipofisário/genética , Mutação , China , Hormônio do Crescimento
19.
Artigo em Inglês | MEDLINE | ID: mdl-38379171

RESUMO

BACKGROUND: The increase in portal insulin levels has been shown to upregulate growth hormone receptor expression in the liver, leading to increased insulin-like growth hormone- 1 levels. Metformin inhibits hepatic gluconeogenesis and reduces fasting insulin. OBJECTIVE: We evaluated the effect of metformin treatment in patients with acromegaly on growth hormone, insulin-like growth hormone-1, and pituitary adenoma size. METHODS: Patients who were followed up with the diagnosis of acromegaly in Istanbul University- Cerrahpasa, Cerrahpasa Medical Faculty were evaluated. The patients were divided into three groups after pituitary adenectomy as those who received somatostatin receptor ligand and metformin treatment (group A), somatostatin receptor ligand treatment only (group B), and those who received metformin treatment only (group C). Groups A and B were compared with each other, and patients in group C were compared among themselves. RESULTS: While the median insulin-like growth factor-1 level decreased to 170 ng/ml in Group A after the treatment, the median insulin-like growth factor-1 level decreased to 229 ng/ml in Group B, and a statistically significant difference was found between the two groups (p =0.020). There was no significant difference in post-treatment growth hormone levels and residual adenoma sizes between groups A and B (p >0.005). In group C, there was no significant difference in growth hormone values pre-and post-metformin treatment (p =0.078); however, the median insulin-like growth factor-1 level decreased from 205 ng/ml to 168 ng/ml during metformin treatment and was found to be statistically significant (p =0.027). CONCLUSION: Due to the effect of metformin treatment on insulin-like growth factor-1 values in patients with acromegaly, it can be used in disease control, as well as diabetes treatment.


Assuntos
Acromegalia , Hormônio do Crescimento Humano , Metformina , Humanos , Acromegalia/tratamento farmacológico , Metformina/uso terapêutico , Ligantes , Receptores de Somatostatina , Hormônio do Crescimento , Insulina , Fator de Crescimento Insulin-Like I/metabolismo
20.
Rev Paul Pediatr ; 42: e2023073, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38359318

RESUMO

OBJECTIVE: To assess the effect of recombinant growth hormone (rGH) on body composition and metabolic profile of prepubertal short children born small for gestational age (SGA) before and after 18 months of treatment. METHODS: It is a clinical, non-randomized, and paired study. Children born SGA, with birth weight and/or length <-2 standard deviations (SD) for gestational age and sex, prepubertal, born at full term, of both genders, with the indication for treatment with rGH were included. The intervention was performed with biosynthetic rGH at doses ranging from 0.03 to 0.05 mg/kg/day, administered subcutaneously, once a day at bedtime. Total lean mass (LM) and total fat mass (FM) were carried out using dual-energy X-ray absorptiometry (DXA), and the metabolic profile was assessed for insulin, glycemia, IGF-1 levels and lipid profile. RESULTS: Twelve patients (nine girls, 8.17±2.39 y) were evaluated; three patients dropped out of the study. There was an increase of LM adjusted for length (LMI) (p=0.008), LMI standard deviation score (SDS) adjusted for age and sex (p=0.007), and total LM (p<0.001). The percentage of body fat (BF%) and abdominal fat (AF) remained unaltered in relation to the beginning of treatment. Among the metabolic variables, blood glucose remained within normal levels, and there was a reduction in the number of participants with altered cholesterol (p=0.023). CONCLUSIONS: The effect of rGH treatment was higher on LM than in FM, with increased LM adjusted for length and standardized for age and sex. Glycemia remained within the normal limits, and there was a decreased number of children with total cholesterol above the recommended levels.


Assuntos
Hormônio do Crescimento , Hormônio do Crescimento Humano , Criança , Humanos , Feminino , Masculino , Lactente , Hormônio do Crescimento/farmacologia , Hormônio do Crescimento/uso terapêutico , Idade Gestacional , Hormônio do Crescimento Humano/farmacologia , Hormônio do Crescimento Humano/uso terapêutico , Composição Corporal , Metaboloma , Colesterol/farmacologia , Estatura
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