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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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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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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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GH Supplementation Effects on Cardiovascular Risk in GH Deficient Adult Patients: A Systematic Review and Meta-analysis.
Giagulli, VA, Castellana, M, Perrone, R, Guastamacchia, E, Iacoviello, M, Triggiani, V
Endocrine, metabolic & immune disorders drug targets. 2017;(4):285-296
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BACKGROUND AND OBJECTIVE The current meta-analysis aims at evaluating whether the existing clinical evidence may ascertain the effects of growth hormone (GH) replacement therapy on cardiovascular risk, both in isolated GH deficiency (GHD) and in compensated panhypopituitarism including GH deficit. METHODS Original articles published from 1991 to 2015 were searched on Medline (Pubmed). Among an overall number of 181 potentially suitable studies, 24 fulfilled the selection criteria and were included in the analysis. Data aggregation was carried out through the calculation of the absolute risk reduction. The meta-analysis was then conducted by means of a fixed-effects model, according to the heterogeneity test (Chi-square statistic). RESULTS Fat-free mass (FFM) increase and fat mass (FM) reduction were found, together with a C-LDL reduction, a wide variation in glycaemia and a neutral effect on glycated haemoglobin (HbA1c) and blood pressure. These effects were valid both for isolated GHD patients and for those with compensated panhypopituitarism. The global outcome D showed a nonsignificant reduction of the overall cardiovascular risk (0.53; 95% C.I. -1.23, 2.85). CONCLUSION Our meta-analysis shows no signnificatly positive trend in cardiovascular risk after both short and long-term GH supplementation therapy in adult GHD patients. However, a reduction of LDL cholesterol levels has been found. No differences were found between isolated GHD participants and those affected by panhypopituitarism well compensated since at least 3 months.
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Recovery responses of testosterone, growth hormone, and IGF-1 after resistance exercise.
Kraemer, WJ, Ratamess, NA, Nindl, BC
Journal of applied physiology (Bethesda, Md. : 1985). 2017;(3):549-558
Abstract
The complexity and redundancy of the endocrine pathways during recovery related to anabolic function in the body belie an oversimplistic approach to its study. The purpose of this review is to examine the role of resistance exercise (RE) on the recovery responses of three major anabolic hormones, testosterone, growth hormone(s), and insulin-like growth factor 1. Each hormone has a complexity related to differential pathways of action as well as interactions with binding proteins and receptor interactions. Testosterone is the primary anabolic hormone, and its concentration changes during the recovery period depending on the upregulation or downregulation of the androgen receptor. Multiple tissues beyond skeletal muscle are targeted under hormonal control and play critical roles in metabolism and physiological function. Growth hormone (GH) demonstrates differential increases in recovery with RE based on the type of GH being assayed and workout being used. IGF-1 shows variable increases in recovery with RE and is intimately linked to a host of binding proteins that are essential to its integrative actions and mediating targeting effects. The RE stress is related to recruitment of muscle tissue with the glandular release of hormones as signals to target tissues to support homeostatic mechanisms for metabolism and tissue repair during the recovery process. Anabolic hormones play a crucial role in the body's response to metabolism, repair, and adaptive capabilities especially in response to anabolic-type RE. Changes of these hormones following RE during recovery in the circulatory biocompartment of blood are reflective of the many mechanisms of action that are in play in the repair and recovery process.
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Growth hormone therapy for people with thalassaemia.
Ngim, CF, Lai, NM, Hong, JY, Tan, SL, Ramadas, A, Muthukumarasamy, P, Thong, MK
The Cochrane database of systematic reviews. 2017;(9):CD012284
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BACKGROUND Thalassaemia is a recessively-inherited blood disorder that leads to anaemia of varying severity. In those affected by the more severe forms, regular blood transfusions are required which may lead to iron overload. Accumulated iron from blood transfusions may be deposited in vital organs including the heart, liver and endocrine organs such as the pituitary glands which can affect growth hormone production. Growth hormone deficiency is one of the factors that can lead to short stature, a common complication in people with thalassaemia. Growth hormone replacement therapy has been used in children with thalassaemia who have short stature and growth hormone deficiency. OBJECTIVES To assess the benefits and safety of growth hormone therapy in people with thalassaemia. SEARCH METHODS We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles, reviews and clinical trial registries. Our database and trial registry searches are current to 10 August 2017 and 08 August 2017, respectively. SELECTION CRITERIA Randomised and quasi-randomised controlled trials comparing the use of growth hormone therapy to placebo or standard care in people with thalassaemia of any type or severity. DATA COLLECTION AND ANALYSIS Two authors independently selected trials for inclusion. Data extraction and assessment of risk of bias were also conducted independently by two authors. The quality of the evidence was assessed using GRADE criteria. MAIN RESULTS One parallel trial conducted in Turkey was included. The trial recruited 20 children with homozygous beta thalassaemia who had short stature; 10 children received growth hormone therapy administered subcutaneously on a daily basis at a dose of 0.7 IU/kg per week and 10 children received standard care. The overall risk of bias in this trial was low except for the selection criteria and attrition bias which were unclear. The quality of the evidence for all major outcomes was moderate, the main concern was imprecision of the estimates due to the small sample size leading to wide confidence intervals. Final height (cm) (the review's pre-specified primary outcome) and change in height were not assessed in the included trial. The trial reported no clear difference between groups in height standard deviation (SD) score after one year, mean difference (MD) -0.09 (95% confidence interval (CI) -0.33 to 0.15 (moderate quality evidence). However, modest improvements appeared to be observed in the following key outcomes in children receiving growth hormone therapy compared to control (moderate quality evidence): change between baseline and final visit in height SD score, MD 0.26 (95% CI 0.13 to 0.39); height velocity, MD 2.28 cm/year (95% CI 1.76 to 2.80); height velocity SD score, MD 3.31 (95% CI 2.43 to 4.19); and change in height velocity SD score between baseline and final visit, MD 3.41 (95% CI 2.45 to 4.37). No adverse effects of treatment were reported in either group; however, while there was no clear difference between groups in the oral glucose tolerance test at one year, fasting blood glucose was significantly higher in the growth hormone therapy group compared to control, although both results were still within the normal range, MD 6.67 mg/dL (95% CI 2.66 to 10.68). There were no data beyond the one-year trial period. AUTHORS' CONCLUSIONS A small single trial contributed evidence of moderate quality that the use of growth hormone for a year may improve height velocity of children with thalassaemia although height SD score in the treatment group was similar to the control group. There are no randomised controlled trials in adults or trials that address the use of growth hormone therapy over a longer period and assess its effect on final height and quality of life. The optimal dosage of growth hormone and the ideal time to start this therapy remain uncertain. Large well-designed randomised controlled trials over a longer period with sufficient duration of follow up are needed.
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Challenges in the Management of Short Stature.
Argente, J
Hormone research in paediatrics. 2016;(1):2-10
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Human growth, from fetal life to adolescence, is dynamic and a good marker of health. Growth is a complex process influenced by genetic, hormonal, nutritional and environmental factors, both pre- and postnatally. To date, no international agreement regarding normal height has been established. Auxological parameters are fundamental to investigate potential short stature (SS), either with a known diagnosis, e.g. disproportionate or proportionate, prenatal and/or postnatal onset, or an unknown diagnosis, i.e. idiopathic SS. The incidence/prevalence of SS is difficult to establish. The measurement of choice in children aged <2 years is length, while in those >2 years of age it is height. A number of monogenic diseases that lead to proportionate SS due to either isolated growth hormone deficiency, multiple pituitary hormone deficiency, growth hormone insensitivity, primary acid-labile subunit deficiency, primary IGF-1 deficiency, IGF-1 resistance, primary IGF-2 deficiency or primary protease deficiency have been discovered in the last 30 years. In addition, the Nosology and Classification of Genetic Skeletal Disorders revised in 2015 includes 436 conditions, with a number of genes of 364. A practical algorithm for the evaluation of SS as well as therapeutic options are discussed.
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Prader-Willi syndrome and growth hormone deficiency.
Aycan, Z, Baş, VN
Journal of clinical research in pediatric endocrinology. 2014;(2):62-7
Abstract
Prader-Willi syndrome (PWS) is a rare multisystem genetic disorder demonstrating great variability with changing clinical features during patient's life. It is characterized by severe hypotonia with poor sucking and feeding difficulties in early infancy, followed by excessive eating and gradual development of morbid obesity in later infancy or early childhood. The phenotype is most probably due to hypothalamic dysfunction which is also responsible for growth hormone (GH) and thyroid-stimulating hormone (TSH) deficiencies, central adrenal insufficiency and hypogonadism. The multidimensional problems of patients with PWS can be managed with multidisciplinary approach. Reduced GH secretion, low peak GH response to stimulation, decreased spontaneous GH secretion and low serum IGF-1 levels in PWS patients have been documented in many studies. GH therapy has multiple beneficial effects on growth and body composition, motor and mental development in PWS patients. The recommended dosage for GH is 0.5-1 mg/m2/day. GH therapy should not be started in the presence of obstructive sleep apnea syndrome, adenotonsillar hypertrophy, severe obesity and diabetes mellitus. GH treatment should be considered for patients with genetically confirmed PWS in conjunction with dietary, environmental and life-style measures.
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Determinants of GH resistance in malnutrition.
Fazeli, PK, Klibanski, A
The Journal of endocrinology. 2014;(3):R57-65
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States of undernutrition are characterized by GH resistance. Decreased total energy intake, as well as isolated protein-calorie malnutrition and isolated nutrient deficiencies, result in elevated GH levels and low levels of IGF1. We review various states of malnutrition and a disease state characterized by chronic undernutrition - anorexia nervosa - and discuss possible mechanisms contributing to the state of GH resistance, including fibroblast growth factor 21 and Sirtuin 1. We conclude by examining the hypothesis that GH resistance is an adaptive response to states of undernutrition, in order to maintain euglycemia and preserve energy.
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Clinical review: The human experience with ghrelin administration.
Garin, MC, Burns, CM, Kaul, S, Cappola, AR
The Journal of clinical endocrinology and metabolism. 2013;(5):1826-37
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CONTEXT Ghrelin is an endogenous stimulator of GH and is implicated in a number of physiological processes. Clinical trials have been performed in a variety of patient populations, but there is no comprehensive review of the beneficial and adverse consequences of ghrelin administration to humans. EVIDENCE ACQUISITION PubMed was utilized, and the reference list of each article was screened. We included 121 published articles in which ghrelin was administered to humans. EVIDENCE SYNTHESIS Ghrelin has been administered as an infusion or a bolus in a variety of doses to 1850 study participants, including healthy participants and patients with obesity, prior gastrectomy, cancer, pituitary disease, diabetes mellitus, eating disorders, and other conditions. There is strong evidence that ghrelin stimulates appetite and increases circulating GH, ACTH, cortisol, prolactin, and glucose across varied patient populations. There is a paucity of evidence regarding the effects of ghrelin on LH, FSH, TSH, insulin, lipolysis, body composition, cardiac function, pulmonary function, the vasculature, and sleep. Adverse effects occurred in 20% of participants, with a predominance of flushing and gastric rumbles and a mild degree of severity. The few serious adverse events occurred in patients with advanced illness and were not clearly attributable to ghrelin. Route of administration may affect the pattern of adverse effects. CONCLUSIONS Existing literature supports the short-term safety of ghrelin administration and its efficacy as an appetite stimulant in diverse patient populations. There is some evidence to suggest that ghrelin has wider ranging therapeutic effects, although these areas require further investigation.
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Recombinant growth hormone therapy for cystic fibrosis in children and young adults.
Thaker, V, Haagensen, AL, Carter, B, Fedorowicz, Z, Houston, BW
The Cochrane database of systematic reviews. 2013;(6):CD008901
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BACKGROUND Cystic fibrosis is an inherited condition causing disease most noticeably in the lungs, digestive tract and pancreas. People with cystic fibrosis often have malnutrition and growth delay. Adequate nutritional supplementation does not improve growth optimally and hence an anabolic agent, recombinant growth hormone, has been proposed as a potential intervention. OBJECTIVES To evaluate the effectiveness and safety of recombinant human growth hormone therapy in improving lung function, quality of life and clinical status of children and young adults with cystic fibrosis. SEARCH METHODS We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of latest search: 15 May 2013.We conducted a search of relevant endocrine journals and proceedings of the Endocrinology Society meetings using Scopus and Proceedings First. Date of latest search: 15 March 2012. SELECTION CRITERIA Randomised and quasi-randomised controlled trials of all preparations of recombinant growth hormone compared to either no treatment, or placebo, or each other at any dose (high-dose and low-dose) or route and for any duration, in children or young adults aged up to 25 years diagnosed with cystic fibrosis (by sweat test or genetic testing). DATA COLLECTION AND ANALYSIS Two authors independently screened papers, extracted trial details and assessed their risk of bias. MAIN RESULTS Four controlled trials were included in this review (with 161 participants in total), each with an unclear risk of bias. Analysis of data obtained from these trials shows improvement in height for all comparisons, but improvements in weight and lean tissue mass were only reported in the comparison of standard dose recombinant growth hormone versus no treatment. There is moderate improvement in one parameter of pulmonary function tests, functional vital capacity (per cent predicted) when comparing standard dose recombinant growth hormone and no treatment. Little evidence was found for improvement in quality of life. An improvement in fasting blood glucose levels was reported when comparing rhGH to placebo only. Exercise capacity improved in participants receiving standard dose recombinant growth hormone versus no treatment, but not for any other comparison. There is insufficient evidence to conclude any changes in hospitalisations, antibiotic use or significant adverse effects. AUTHORS' CONCLUSIONS Recombinant growth hormone therapy is effective in improving the intermediate outcomes in height, weight and lean tissue mass when compared with no treatment. One measure of pulmonary function test showed moderate improvement. No significant changes in quality of life, clinical status or side-effects were observed in this review. Long-term, well-designed randomised controlled trials of recombinant growth hormone therapy in patients with cystic fibrosis are required prior to evaluation of human growth hormone treatment for routine use in patients.