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IGF-I deficiency and enhanced insulin sensitivity due to a mutated growth hormone receptor gene in humans.
Guevara-Aguirre, J, Torres, C, Peña, G, Palacios, M, Bautista, C, Guevara, A, Gavilanes, AW
Molecular and cellular endocrinology. 2021;:111044
Abstract
Human size is achieved by the coordinated expression of many genes. From conception to adulthood, a given genomic endowment is modified by highly variable environmental circumstances. During each stage of a person's life, distinct nutritional and hormonal influences continuously shape growing physical features until mature characteristics are attained. Underlying processes depend on precise provision of substrates and energy extracted by insulin action from nutrients, which allows cell proliferation, differentiation, and survival, under the concerted actions of growth hormone and insulin-like growth factor-I (IGF-I). It should be noted that growth and metabolic signaling pathways are interdependent and superimposed at multiple levels. Attainment of a fully developed human phenotype should be considered as a harmonious increment in body size rather than a simple increase in height. From this perspective we herein analyze adult features of individuals with an inactive growth hormone receptor, who consequently have severely diminished concentrations of serum insulin and endocrine IGF-I.
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2.
A challenging TSH/GH co-secreting pituitary adenoma with concomitant thyroid cancer; a case report and literature review.
Yoon, JH, Choi, W, Park, JY, Hong, AR, Kim, SS, Kim, HK, Kang, HC
BMC endocrine disorders. 2021;(1):177
Abstract
BACKGROUND Thyroid stimulating hormone (TSH) secreting pituitary adenoma (TSHoma) with coexisting thyroid cancer is extremely rare, and proper treatment of both diseases may pose a unique clinical challenge. When TSHoma has plurihormonality, particularly involving the co-secretion of growth hormone (GH), management can be more complicated. Herein, we present a difficult-to-manage case of papillary thyroid cancer with an incurable TSH/GH-secreting pituitary adenoma. CASE PRESENTATION A 59-year-old man was referred to our hospital due to memory impairment and inappropriate TSH level. Sella magnetic resonance imaging revealed a huge pituitary mass extending to the suprasellar area. Clinical diagnosis of TSH/GH co-secreting pituitary adenoma was made based on elevated free T4, total T3, serum α-subunit, insulin-like growth factor-1 levels and non-suppressible GH levels after oral glucose loading. Rectal cancer and multifocal papillary thyroid microcarcinoma (PTMC) were diagnosed during initial screening for internal malignancy; lower anterior resection was performed and close observation was planned for PTMC. Long-acting octreotide therapy was commenced, which resulted in a dramatic reduction in TSHoma size and facilitated control of hormonal excess. Total thyroidectomy and radioactive iodine (RAI) therapy were needed during follow up due to the growth of PTMC. After the surgery, the pituitary adenoma represented resistance to somatostatin analogue therapy and the tumor size gradually increased despite the addition of dopamine agonist therapy. Furthermore, TSH suppressive therapy with levothyroxine was impossible and an adequate TSH level for RAI therapy was unmountable. Late debulking pituitary surgery was ineffective, and the patient gradually deteriorated and lost to follow up. CONCLUSION We report the first aggravated case of TSH/GH co-secreting pituitary tumor after total thyroidectomy for concomitant multifocal PTMC. Deferring of thyroid surgery until the TSHoma is well controlled may be the optimal therapeutic strategy in patients with TSHoma and coexistent thyroid cancer; ablative thyroid surgery may result in catastrophic pituitary tumor growth.
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3.
[Acromegaly and it's cardiovascular implications].
Cadena-Obando, DA, Remba-Shapiro, I, Abreu-Rosario, CG, Mercado, M
Revista medica del Instituto Mexicano del Seguro Social. 2021;(1):73-80
Abstract
Acromegaly is a chronic and slowly progressive disease that results from the hypersecretion of growth hormone (GH) and consequently insulin-like growth factor type 1 (IGF-1), due to a GH-secreting pituitary adenoma in 95-98% of cases. There are several complications or co-morbidities associated with acromegaly, the most frequent being cardiovascular, metabolic and neoplastic. The cardiovascular complications of acromegaly go from arterial hypertension to a peculiar form of cardiomyopathy and are the result of the long-standing exposure to high GH and IGF-1 levels. The pathophysiology of these complications is complex and includes an increased tubular reabsorption of sodium and the direct effects of GH and IGF-1 on the endothelium and the cardiac tissue itself. Frequently, the cardiovascular comorbidities of acromegaly occur concomitantly with metabolic complications such as diabetes and respiratory abnormalities such as the sleep apnea syndrome. In this brief review we analyze the pathophysiology, the clinical manifestations and the management of the cardiovascular complications of acromegaly.
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MANAGEMENT OF ENDOCRINE DISEASE: Etiology and outcome of acromegaly in patients with a paradoxical GH response to glucose.
Hage, M, Janot, C, Salenave, S, Chanson, P, Kamenický, P
European journal of endocrinology. 2021;(6):R261-R268
Abstract
To gain more insight on the pathogenesis of somatotroph pituitary adenomas, recent studies have focused on a subgroup of patients with acromegaly displaying a paradoxical growth hormone (GH) response during oral glucose tolerance test (OGTT). The paradoxical rise of GH after oral glucose intake occurs in about one-third of acromegaly patients and has been pathogenetically linked, by analogy to glucose-dependent insulinotropic polypeptide (GIP)-dependent Cushing's syndrome, to the ectopic expression of GIP receptor (GIPR) in somatotroph adenoma cells. GIPR-expressing adenomas are negative for activating GNAS gene mutations and display distinct cytogenetic and DNA methylation profiles, highlighting their unique molecular pathogenesis. Acromegaly patients with a paradoxical GH response pattern seem to display higher insulin-like growth factor-1 (IGF-1) concentrations and harbour smaller adenomas that are more often of the densely granulated phenotype. They seem also to show a better response to somatostatin receptor ligands. In addition, persistent paradoxical GH response after surgery may be a biological marker of the residual disease postoperatively. Targeted therapy to antagonize GIP receptor on GIPR-expressing somatotroph adenomas could be a new treatment approach for acromegaly patients with a paradoxical pattern of GH response to OGTT.
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5.
Effects of nutrition and hormones on functional appliance treatment outcome in patients with skeletal Class II malocclusion.
Zhang, X, Yi, J, Li, Y
Journal of the World federation of orthodontists. 2020;(1):9-12
Abstract
BACKGROUND Functional appliances has been used for treatment of skeletal Class II malocclusion for a long time; however, the real skeletal effects, mandibular growth particularly, remain insufficient. Several auxiliary approaches have been attempted with the hope of enhancing treatment effects. In this review, we summarize and discuss the use of additional nutrition and hormones to assist the functional appliance treatment on patients with skeletal Class II malocclusion. METHODS Relevant articles were identified by electronic research in MEDLINE Ovid using keywords such as "nutrition," "hormone," "functional appliance," "orthodontics," "maxillofacial development," and "maxillofacial abnormalities." References of related articles were assessed for relevant studies to identify additional published references. RESULTS The literature search yielded 239 studies. According to the current literature, use of additional nutrition and hormones, including growth hormones, sex hormones, insulin, and insulin-like growth factor I, seem to improve the effects of functional appliance treatment on patients with skeletal Class II malocclusion. CONCLUSIONS The current evidence indicates that additional nutrition or hormones might improve the treatment effects on mandibular hypoplasia compared with the functional appliance alone, which is a promising approach and calls for further studies.
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The enigmatic role of growth hormone in age-related diseases, cognition, and longevity.
Colon, G, Saccon, T, Schneider, A, Cavalcante, MB, Huffman, DM, Berryman, D, List, E, Ikeno, Y, Musi, N, Bartke, A, et al
GeroScience. 2019;(6):759-774
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Abstract
Growth hormone (GH) is secreted by the anterior pituitary gland and regulates various metabolic processes throughout the body. GH and IGF-1 levels are markedly reduced in older humans, leading some to hypothesize GH supplementation could be a viable "anti-aging" therapy. However, there is still much debate over the benefits and risks of GH administration. While an early study of GH administration reported reduced adiposity and lipid levels and increased bone mineral density, subsequent studies failed to show significant benefits. Conversely, other studies found positive effects of GH deficiency including extended life span, improved cognitive function, resistance to diseases such as cancer and diabetes, and improved insulin sensitivity despite a higher fat percentage. Thus, the roles of GH in aging and cognition remain unclear, and there is currently not enough evidence to support use of GH as an anti-aging or cognitive impairment therapy. Additional robust and longer-duration studies of efficacy and safety of GH administration are needed to determine if modulating GH levels could be a successful strategy for treating aging and age-related diseases.
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Biomarkers of GH action in children and adults.
Schilbach, K, Olsson, DS, Boguszewski, MCS, Bidlingmaier, M, Johannsson, G, Jørgensen, JL
Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. 2018;:1-8
Abstract
Growth hormone (GH) and IGF-I levels in serum are used as biomarkers in the diagnosis and management of GH-related disorders but have not been subject to structured validation. Auxological parameters in children and changes in body composition in adults, as well as metabolic parameters and patient related outcomes are used as clinical and surrogate endpoints. New treatment options, such as long acting GH and GH antagonists, require reevaluation of the currently used biochemical biomarkers. This article will review biomarkers, surrogate endpoints and clinical endpoints related to GH treatment in children and adults as well as in acromegaly.
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Treatment with growth hormone in the prader-willi syndrome.
Moix Gil, E, Giménez-Palop, O, Caixàs, A
Endocrinologia, diabetes y nutricion. 2018;(4):229-236
Abstract
INTRODUCTION The Prader-Willi syndrome (PWS) is a rare genetic disorder caused by absence of expression of the paternal alleles in región 15q11.2-q13. Obesity and hormonal deficiencies, especially of growth hormone (GH), are the most important signs from the therapeutic viewpoint. Recombinant GH (rGH) is effective in children and represents the mainstay in treatment; by contrast, little evidence in available in adult patients. OBJECTIVE To review the reported evidence on the beneficial and adverse effects of treatment with rGH in children and adults. DESIGN A review was made of 62 original articles published between 2000 and 2017 using the PubMed database. RESULTS In pediatric and adult PWS, rGH improves body morphology and composition, physical performance, cognition, psychomotor development, respiratory function, and quality of life with few adverse effects. CONCLUSIONS Treatment with rGH is effective and safe and improves quality of life in both children and adults with PWS.
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Diagnosis of GH Deficiency as a Late Effect of Radiotherapy in Survivors of Childhood Cancers.
Sfeir, JG, Kittah, NEN, Tamhane, SU, Jasim, S, Chemaitilly, W, Cohen, LE, Murad, MH
The Journal of clinical endocrinology and metabolism. 2018;(8):2785-2793
Abstract
BACKGROUND Limited guidance exists for selecting a laboratory method for diagnosing GH deficiency (GHD) when it occurs as a late effect of radiotherapy in childhood cancer survivors (CCSs). METHODS We searched Medline, Embase, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, and Scopus for studies evaluating GHD that used IGF-1 or IGF-binding protein 3 (IGFBP-3) measurements compared with GH dynamic testing. RESULTS We included 15 studies [IGF-1 (8 studies) and IGFBP-3 (7 studies)] enrolling 477 patients. Comparator tests varied widely. Overall, both IGF-1 and IGFBP-3 had suboptimal diagnostic accuracy but were strongly correlated. The use of both tests simultaneously in the same cohort did not improve the diagnostic accuracy. Despite high variability in the testing protocols, dynamic tests remained the most accurate for appropriately identifying patients with GHD. The insulin tolerance test (ITT) appears to be the most accepted reference test when used alone or in combination with arginine; however, standardized testing strategies among practice groups are absent. GHRH and arginine stimulation performed almost similarly to the ITT; however, in one study GHRH with arginine stimulation had 66% sensitivity and 88% specificity compared with the ITT. Insufficient data were available to assess the accuracy of serial GH testing (nocturnal or over 24 hours). CONCLUSION The diagnostic accuracy of various dynamic tests for GHD in CCSs appears to follow the same patterns as those in non-CCSs. Interpreting GHRH stimulation is a challenge given the primarily hypothalamic dysfunction in CCSs. IGF-1 and IGFBP-3 perform poorly in this population.
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The Physiology of Childhood Growth: Hormonal Regulation.
Benyi, E, Sävendahl, L
Hormone research in paediatrics. 2017;(1):6-14
Abstract
The growth patterns of a child changes from uterine life until the end of puberty. Height velocity is highest in utero and declines after birth until puberty when it rises again. Important hormonal regulators of childhood growth are growth hormone, insulin-like growth factor 1, sex steroids, and thyroid hormone. This review gives an overview of these hormonal regulators of growth and their interplay with nutrition and other key players such as inflammatory cytokines.