|Year : 2015 | Volume
| Issue : 2 | Page : 245-251
Insulin-like growth factor- I and factors affecting it in thalassemia major
Ashraf T Soliman1, Vincenzo De Sanctis2, Rania Elalaily3, Mohamed Yassin4
1 Department of Pediatric, Pediatric Endocrinology Division, Alamal Hospital, Hamad Medical Center, Qatar
2 Pediatric and Adolescent Outpatient Clinic, Quisisana Hospital, Ferrara, Italy
3 Family Medicine, Primary Health Care, Doha, Qatar
4 Department of Hematology and Oncology, Alamal Hospital, Hamad Medical Center, Qatar
|Date of Web Publication||14-Jan-2015|
Ashraf T Soliman
Department of Pediatric, Hamad Medical Center, Doha
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Despite improvement of blood transfusion regimens and iron chelation therapy growth and maturational delay, cardiomyopathy, endocrinopathies and osteoporosis still occur in good number of thalassemic patients. Decreased IGF-1 secretion occurs in the majority of the thalassemic patients particularly those with growth and pubertal delay. Many factors contribute to this decreased synthesis of IGF-I including disturbed growth hormone (GH) - insulin-like growth factor - I (IGF-I) axis. The possible factors contributing to low IGF-I synthesis in thalassemia and the possible interaction between low IGF-I secretion and the occurrence of these complications is discussed in this mini-review. Improvement of IGF-I secretion in thalassemic patients should be intended to improve linear growth and bone mineral accretion in thalassemic patients. This can be attained through adequate correction of anemia and proper chelation, nutritional supplementation (increasing caloric intake), correction of vitamin D and zinc deficiencies, induction of puberty and correction of hypogonadism at the proper time and treating GH deficiency. This review paper provides a summary of the current state of knowledge regarding IGF-I and factors affecting it in patients with thalassaemia major (TM). Search on PubMed and reference lists of articles with the term 'IGF-I, GH, growth, thalassemia, thyroxine, anemia, vitamin D, and zinc' was carried out. A hundred and forty-eight articles were found and used in the write up and the data analyzed was included in this report.
Keywords: Anemia, ferritin, growth hormone, growth, Insulin-like growth factor-I, nutrition, puberty, thalassemia, thyroxine, vitamin D, zinc
|How to cite this article:|
Soliman AT, Sanctis VD, Elalaily R, Yassin M. Insulin-like growth factor- I and factors affecting it in thalassemia major. Indian J Endocr Metab 2015;19:245-51
|How to cite this URL:|
Soliman AT, Sanctis VD, Elalaily R, Yassin M. Insulin-like growth factor- I and factors affecting it in thalassemia major. Indian J Endocr Metab [serial online] 2015 [cited 2020 Jun 1];19:245-51. Available from: http://www.ijem.in/text.asp?2015/19/2/245/131750
| Introduction|| |
Growth and maturational delay are striking features of beta-thalassaemia major (BTM). After the age of four years, growth faltering sets in but becomes obvious after the age of eight years that involves stature, sitting height, weight and skeletal maturation. After this age, a slowing down of growth and a reduced or absent pubertal growth spurt are observed. There is marked attenuation or loss of pubertal growth spurt and the growth plate fusion is usually delayed until the end of the second decade of life.
The pathogenesis of growth failure is multi-factorial and is mainly due to chronic anemia and hypoxia, iron overload of different organs, chronic liver disease, nutritional deficiency, inadequate use of chelating agents and endocrinopathies (hypogonadism, delayed puberty, hypothyroidism and GH-IGF-1 axis deregulations). ,,,
Insulin-like growth factor-I (IGF-I) is the major mediator of (GH)-stimulated somatic growth and a mediator of GH-independent anabolic responses in many cells and tissues. It is synthesized by multiple mesenchymal cell types, and mediates most of the physiological actions of GH and is the major effector of bone growth. ,,,,
Two major mechanisms regulates IGF-I secretion. The endocrine part of IGF-I, which is mainly synthesized in the liver and secreted into the blood, is under the control of growth hormone (GH). Locally produced IGF-I (the autocrine/paracrine part of IGF-I) is important in the activity of several organ systems. This is controlled by GH and by other factors that are secreted locally by the surrounding cell types. Growth hormone, parathyroid hormone (PTH), and sex steroids regulate the production of IGF-I in bone.
Sex steroids are the main regulators of local production of IGF-I in the reproductive system. However, some of the autocrine/paracrine IGF-I that is secreted enters into the systemic circulation. ,,,,,,
After birth, IGF-I appears to have the predominant role in regulating growth and differentiation of functions. It binds specifically to high-affinity membrane-associated receptors that are tyrosine kinases.  During childhood, IGF-I increases progressively and reaches the maximum during puberty (between 12 and 16 years) corresponding to the pubertal growth spurt, and then decreases gradually with age. ,
Liver derived circulating IGF-I and local bone-derived IGF-I overlap in their growth-promoting effects and may replace each other in the maintenance of normal longitudinal bone growth. In contrast, locally derived IGF-I cannot replace liver-derived IGF-I for the regulation of GH secretion, cortical bone mass, kidney size, liver size, prostate size and insulin sensitivity. ,,
In population-based cohort studies, higher IGF-I levels predicted greater childhood height gains and higher levels of insulin secretion for the degree of insulin sensitivity.  Hence it is hypothesized that alterations in IGF-I regulation can provide an attractive explanation for thalassaemia-associated growth impairment. The most potent regulator of IGF-I expression in postnatal life is GH. On the other hand IGF-I mediates growth hormone negative feedback. Additionally, other hormones e.g. insulin, sex-steroids and thyroxin as well as nutrition play important role in IGF-I regulation. ,,
Growth hormone- IGF-I axis in thalassemia
Growth hormone deficiency (GHD) in BTM patients can explain in part low IGF-I synthesis. However, in numerous cross-sectional studies, patients with BTM at different ages who have normal GH secretion (GHS) still have high prevalence of low serum IGF-1 and IGFBP3. ,,
In a longitudinal study, the age-related changes in serum IGF-I concentrations in thalassemic subjects (n = 20), compared to normal standards for age and sex, showed significantly lower IGF-I concentrations from early childhood to 18 years of age. Thalassemic children with GHD did not show any peak of IGF-I level till the age of 18 years. Thalassemic males with GHS achieved their peak IGF-I level late (at 16-18 years of age) whereas normal males (at 13 years of age) and their peak IGF-I level was attenuated (3 times from infancy to puberty vs 8-9 times in normal males). In addition, no statistical differences in age, height standard deviation score (HSDS), target HSDS and bone-age between thalassemic patients with GHD and those with GHS.  The basal IGF-I levels did not differ between the 2 groups at different ages until the age of 12 years. After 12 years of age, IGF-I levels were significantly higher in thalassemic children with GHS vs those with GHD. , These significantly lower age-related longitudinal changes in IGF-I secretion and attenuation at its peak during pubertal years corresponds to the slow growth pattern of thalassemic patients during childhood that is exaggerated during adolescence.
In addition, children with BTM had a significant, but lower IGF-I response after GH administration, compared with the IGF-I response in the GHD.  Many thalassemic children with normal GH response to provocation had low IGF-I secretion suggesting a degree of neuro-secretory dysfunction or decreased GH sensitivity in the liver. The percent increment of IGF-I level in response to exogenous GH stimulation was lower in thalassemic patients vs those with GHD. 
Studying the spontaneous nocturnal GH secretory pulse-pattern has demonstrated neuro-secretory dysfunction in some thalassemic patients with normal GH response to stimulation and low IGF-I. ,,,,,,, Moreover, the low basal GH level in these children in the presence of low IGF-I concentrations suggested an additional disturbance in the (centrally mediated) negative feedback mechanism. 
Although exogenous administration of GH has improved the growth rate and increased circulating IGF-1, concentration in children with BTM with normal GH secretion, and their growth rate was less than that seen in GH-deficient children treated with GH. These data suggest that thalassemic patients had some degree of GH insensitivity. , However, serum GH-binding protein (GHBP) level was normal in short thalassemic patients without GH deficiency ruling significant GH receptor defect.  One study reported decreased IGF-I binding to its cellular receptors in short thalassemic patients vs those with normal stature. 
Puberty and GH- IGF-I axis in thalassemia
Puberty, spontaneous, precocious that are pharmacologically induced has profound effects on the physiology of the GH/IGF-I axis. Both spontaneous and stimulated GH secretion increase with puberty. The increase in spontaneous GH secretion is the result of increased GH pulse amplitude. Analogous to the increase in GH secretion at puberty, circulating IGF-I and IGF binding protein-3 also increase. The pubertal increase in IGF-I correlates with stages of puberty as well as sex steroid levels. GH, IGF-1 and sex steroids all markedly increase during puberty and their actions are amplified mutually to mediate the pubertal growth spurt, and increase muscle mass and mineralization of the skeleton. ,
Delayed and/or failure of puberty due to hypo gonadotropic hypogonadism with or without gonadal dysfunction is common in patients with thalassaemia with consequent deﬁciency of sex steroids. Hypogonadism is associated with low IGF-I secretion and can inﬂuence growth through the modulation of IGF-I induced cellular response and these effects can explain the loss and/or attenuation of pubertal growth spurt in BTM patients. ,,, Thalassemic patients treated with androgen and/or human chorionic gonadotropin (HCG), to stimulate puberty have increased IGF-I levels associated with significant acceleration of growth. 
Moreover, deprivation of GH and IGF-I delay the timely onset of puberty; slow the pace of pubertal maturation; attenuate phallic growth (human); and reduce adult testicular size. In thalassemic patients, low IGF-I may contribute to all of these pathologic features. 
Effect of anemia on IGF-I secretion in thalassemia
Correction of anemia by packed red cell transfusion increases IGF-I secretion and improves linear growth in thalassemic children. However, increased level of Hb is inadequate to increase the level of GH secretion or IGF-I response to exogenous GH. These studies indicate that the effect of increasing Hb concentration on IGF-I secretion explains partial improvement of growth in well-transfused thalassemic children. ,
Nutrition and IGF I in thalassemia
Nutrition is a major factor in growth and development. Low body weight, BMI, mid-arm circumference and skin fold thickness as well as low plasma values of essential amino acids are features of children with thalassemia suggesting a form of under-nutrition. Increased energy expenditure secondary to hyper-metabolism with or without heart failure, nutritional deprivation with or without feeding difficulties arising from fatigue, breathlessness and psychological problems and gastrointestinal hypoxia have been proposed as etiologic factors. In a prospective controlled study, children with thalassaemia major who received high caloric diet had significantly increased IGF-I levels, BMI, mid-arm circumference and skin fold thickness. ,,
Vitamin D Deficiency and IGF-I in thalassemia
Vitamin D deficiency was detected in 50-100% of thalassemic adolescents. An IM injection of a mega dose of cholecalciferol is an effective therapy for treatment for 3 months. Vitamin D has been shown to increase circulating IGF-I and IGFBP-3 with the consistent finding of a positive correlation between vitamin D and IGF-I serum values in population-based cohorts of healthy subjects. Moreover, in children and adolescents, vitamin D deficiency can decrease IGF-I synthesis and their replacement has been associated with increased IGF-I synthesis and improved growth in thalassemic patients. ,,,,
Zinc deficiency and IGF-I in thalassemia
Zinc deficiency is observed in many thalassemic patients due to chronic hemolysis, desferrioxmine therapy and increased urinary excretion. , Zinc deficiency might contribute to delayed growth and decreased IGF-I synthesis in these patients. ,, In fact, zinc supplementation can increase hepatic synthesis of IGF-I and is reported to increase linear growth in thalassemic patients. 
Chelation, liver and serum ferritin level, and IGF-I secretion in thalassemia
Stature growth appears to be significantly associated with the quality of chelation therapy during the prepubertal years in thalassemia.
Studies show that the state of chelation, as reflected by serum ferritin level, significantly affects growth and final height in thalassemic patients. Those with higher serum ferritin grow slower and become shorter adults than those with lower ferritin concentrations. ,,,,,, Recent data from our group show that IGF-I concentrations are correlated significantly with serum ferritin levels, the latter are correlated with hepatic enzyme levels (ALT and AST). These indicate that liver dysfunction, secondary to iron overload and/or hepatitis, may negatively affect growth in thalassemic patients through defective hepatic IGF-I synthesis. Alternatively, certain hepatic complications, chiefly those of nutritional and metabolic in nature (insulin resistance, malnutrition, osteopenia, hypogonadism), may be or partly related to this IGF-I deficiency. 
Hepatic stellate cells are stimulated by IGF-1 and high IGF-1 levels attenuate fibro genesis and accelerate liver regeneration. This effect is mainly mediated by upregulation of hepatic growth factor and downregulation of transforming growth factor β1. Thus, decreased IGF-1 levels in thalassemic patients may impair regeneration potential in patients with chronic hepatitis, cirrhosis, or fibrosis. 
Thyroid and IGF-I in thalassemia
The frequency of hypothyroidism in thalassemia patients ranges from 6 to 30% among different countries depending on chelation regimens. Progressive worsening of thyroid function is observed in 35% of thalassemic patients by the age of 18 years. 
Thyroid hormones are among the important direct biological regulators of growth plate and bone accretion. In addition, thyroid hormones influence and interact with the GH - IGF-I system and other hormones that control stature and bone growth. Hypothyroid patients show low plasma levels of IGF-I and reduced IGF bioactivity. Besides, a hypothyroidism is associated with decrease in hepatic IGF-I messenger RNA (mRNA) expression. Correction of hypothyroidism is associated with increased IGF-I secretion and improved linear growth. ,
Parathyroid and IGF-I in thalassemia
Hypoparathyroidism is one of the important complications of BTM due to iron deposition notably in the second decade of life. The prevalence varies greatly from very low i.e. 4% to as high as 27%. , IGF-I and PTH have synergistic actions on bone and some effects of the anabolic actions of PTH are mediated by local production of IGF-I, as has been shown in vitro and in vivo studies both in animals and humans.  Therefore, prevention and treatment of hypoparathyroidism can possibly improve bone anabolism through increasing secretion and/or action of IGF-I.
IGF-I and osteoporosis in thalassemia
Osteoporosis and decreased bone mineral density has been described extensively in children and adult thalassemics. IGF-1 has a fundamental role to stimulate osteoblastic function and bone formation. IGF-1 has modest effects on the proliferation of cells of the osteoblastic lineage and enhances the function of the mature osteoblast.  Additionally, IGF-1 upregulates collagen synthesis and decreases its degradation, which is important for maintaining the appropriate levels of bone matrix and bone mass. In addition, osteoclasts express IGF-1 receptors and IGF-1 has direct effects on their function.  Defective GH - IGF-I secretion contributes to osteoporosis and demineralization in TM patients. , In thalassemic children, bone mineral density is correlated with the circulating concentrations of IGF-I and IGFBP3, as well as with the auxanologic parameters (age, weight, height, HSDS, and BMI). It is suggested that increasing the circulating IGF-I concentration through aggressive nutritional therapy and/or GH/IGF-I therapy with supplementation of vitamin D and/or calcium might improve bone growth and mineralization and prevent the development of osteoporosis and consequent fractures in these patients. 
IGF-I and heart in thalassemia
Heart disease represents the main determinant of survival in BTM. Cardiac involvement in thalassemia major (TM) is mainly characterized by left ventricular dysfunction caused by iron overload.  Heart remodeling with increased interstitial fibrosis and heart failure is persistent even with optimal chelation in BTM patients. 
IGF-I possesses specific myocardial receptors and is able to promote cardiac remodeling and even inotropic effects in both humans and other animals. In fact, reduced cardiac mass and performance are present in GH deficiency and these alterations are counteracted by recombinant human GH replacement, restoring IGF-I levels. Recently, the acute administration of 60 μg/kg of rhIGF-I has also been reported to improve cardiac performance evaluated by echocardiography or impedance cardiography in normal subjects.  The potential use of IGF-I therapy for thalassemic patients with heart failure has not yet been demonstrated.
| Conclusion|| |
Decreased IGF-1 secretion occurs in the majority of thalassemic patients especially those with growth and pubertal delay. Many factors contribute to this decreased synthesis of IGF-I including: [Figure 1].
|Figure 1: Etiology and pathological effects of low IGF-I secretion in thalassemic patients (From: Ashraf T Soliman, 2013)|
Click here to view
- GH deficiency, neurosecretory dysfunction of GH and partial resistance to GH (hepatic siderosis and bone), and/or IGF-I resistance
- Delayed and/or failure of puberty due to hypogonadism with lack of stimulatory actions of sex steroids on pituitary release of GH and hepatic release of IGF-I and attenuation of pubertal growth spurt
- Under-nutrition due to hyper-metabolism with a degree of caloric deficiency (macronutrient deficiency) or micronutrient deficiency (vitamin D, zinc) can impair IGF-I synthesis
- Insufficient blood transfusion with significant periods of anemia
- Inadequate iron chelation with iron overload of the pituitary gland (GH, LH, FSH, TSH deficiencies), liver (systemic IGF-I deficiency) and growth plate (local IGF-I deficiency) and the co-occurrence of other endocrine disorders such as hypothyroidism and diabetes mellitus.
Improvement of IGF-I secretion should be aimed at to improve linear growth and bone mineral accretion in thalassemic patients through adequate correction of anemia and proper chelation, nutritional supplementation (increasing caloric intake), correction of vitamin D and zinc deficiencies, induction of puberty and correction of hypogonadism and hypothyroidism at the proper time and treating GH deficiency.
| References|| |
Anita S. Growth retardation in thalassemia major patients. Int J Hum Genet 2003;3:237-46.
Soliman AT, elZalabany MM, Amer M, Ansari BM. Growth and pubertal development in transfusion-dependent children and adolescents with thalassaemia major and sickle cell disease: A comparative study. J Trop Pediatr 1999;45:23-30.
Noetzli LJ, Panigrahy A, Mittelman SD, Hyderi A, Dongelyan A, Coates TD, et al
. Pituitary iron and volume predict hypogonadism in transfusional iron overload. Am J Hematol 2012;87:167-71.
De Sanctis V, Eleftheriou A, Malaventura C, Thalassaemia International Federation Study Group on Growth and Endocrine Complications in Thalassaemia. Prevalence of endocrine complications and short stature in patients with thalassemia major: A multicenter study by Thalassemia International Federation (TIF). Pediatr Endocrinol Rev 2004;2:249-55.
Schoenle E, Zapf J, Humbel RE, Froesch ER. Insulin-like growth factor I stimulates growth in hypophysectomized rats. Nature 1982;296:252-3.
Underwood LE, Van Wyk JJ. Normal and aberrant growth. In: Wilson JD, Foster DW, editors. Williams' Textbook of Endocrinology. 8 th
ed. Philadelphia: Saunders; 1992. p. 1079-138.
Blum WF, Albertsson-Wikland K, Rosberg S, Ranke MB. Serum levels of insulin-like growth factor I (IGF-I) and IGF binding protein 3 reflect spontaneous growth hormone secretion. J Clin Endocrinol Metab 1993;76:1610-6.
Baker J, Liu JP, Robertson EJ, Efstratiadis A. Role of insulin-like growth factors in embryonic and postnatal growth. Cell 1993;75:73-82.
Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: Biological actions. Endocr Rev 1995;16:3-34.
Giordano R, Lanfranco F, Bo M, Pellegrino M, Picu A, Baldi M, et al
. Somatopause reflects age-related changes in the neural control of GH/IGF-I axis. J Endocrinol Invest 2005;28:94-8.
Adamo M, Roberts CT Jr, Le Roith D. Insulin and insulin-like growth factors in health and disease. In: Bittar EE, Bittar N, editors. Principles of Medical Biology: Molecular and Cellular Endocrinology. Vol. 10B. Greenwich: JAI Press; 1997. p. 339-64.
Le Roith D, Butler AA. Insulin-like growth factors in pediatric health and disease. J Clinical Endocrinol Metab 1999;84:4355-61.
LeRoith D. Clinical relevance of systemic and local IGF-I: Lessons from animal models. Pediatr Endocrinol Rev 2008;5:739-43.
LeRoith D, Yakar S. Mechanisms of disease: Metabolic effects of growth hormone and insulin-like growth factor 1. Nat Clin Pract Endocrinol Metab 2007;3:302-10.
Pennisi PA, Kopchick JJ, Thorgeirsson S, LeRoith D, Yakar S. Role of growth hormone (GH) in liver regeneration. Endocrinology 2004;145:4748-55.
Spiteri-Grech J, Weinbauer GF, Bolze P, Chandolia RK, Bartlett JM, Nieschlag E. Effects of FSH and testosterone on intratesticular insulin-like growth factor-I and specific germ cell populations in rats treated with gonadotrophin-releasing hormone antagonist. J Endocrinol 1993;137:81-9.
Wit JM, Camacho-Hübnerb C. Endocrine regulation of longitudinal bone growth. Endocr Dev 2011;21:30-41.
Friedrich N, Alte D, Völzke H, Spilcke-Liss E, Lüdemann J, Lerch MM, et al
. Reference ranges of serum IGF-1 and IGFBP-3 levels in a general adult population: Results of the Study of Health in Pomerania (SHIP). Growth Horm IGF Res 2008;18:228-37.
Kanbur NO, Derman O, Kinik E. The relationships between pubertal development, IGF-1 axis, and bone formation in healthy adolescents. J Bone Miner Metab 2005;23:76-83.
Ohlsson C, Mohan S, Sjögren K, Tivesten A, Isgaard J, Isaksson O, et al
. The role of liver-derived insulin-like growth factor-I. Endocr Rev 2009;30:494-535.
Sjögren K, Jansson JO, Isaksson OG, Ohlsson C. A transgenic model to determine the physiological role of liver-derived insulin-like growth factor I. Minerva Endocrinol 2002;27:299-311.
Laron Z. Insulin-like growth factor 1 (IGF-1): A growth hormone. Mol Pathol 2001;54:311-6.
Camacho-Hubner C. Normal physiology of growth hormone and insulin-like growth factors in childhood. In: Endotext.com. Ch. 5a, Feb. 2010. Available from: http://www.endotext.org/neuroendo/neuroendo5a/neuroendoframe5a.htm [Last accessed on 2013 Oct 31].
Parker EA, Hegde A, Buckley M, Barnes KM, Baron J, Nilsson O. Spatial and temporal regulation of GH-IGF-related gene expression in growth plate cartilage. J Endocrinol 2007;194:31-40.
Löfqvist C, Andersson E, Gelander L, Rosberg S, Hulthen L, Blum WF, et al
. Reference values for insulin-like growth factor-binding protein-3 (IGFBP-3) and the ratio of insulin-like growth factor-I to IGFBP-3 throughout childhood and adolescence. J Clin Endocrinol Metab 2005;90:1420-7.
Iñiguez G, Ong K, Bazaes R, Avila A, Salazar T, Dunger D, et al
. Longitudinal changes in insulin-like growth factor-I, insulin sensitivity, and secretion from birth to age three years in small-for-gestational-age children. J Clin Endocrinol Metab 2006;91:4645-9.
Soliman AT, El Banna N, Ansari BM. GH response to provocation and circulating IGF-I and IGF-binding protein-3 concentrations, the IGF-I generation test and clinical response to GH therapy in children with beta-thalassaemia. Eur J Endocrinol 1998;138:394-400.
Soliman AT, Abushahin A, Abohezeima K, Khalafallah H, Adel A, Elawwa A, et al
. Age related IGF-I changes and IGF-I generation in thalassemia major. Pediatr Endocrinol Rev 2011;8:278-83.
Shehadeh N, Hazani A, Rudolf MC, Peleg I, Benderly A, Hochberg Z Neurosecretory dysfunction of growth hormone secretion in thalassemia major. Acta Paediatr Scand 1990;79:790-5.
Spiliotis BE, Chrysis DC, Alexandrides TK, Georgopoulos N, Koromantzou EV, Beratis NG. IGF-I generation test as a potential marker of growth hormone neurosecretory dynamics in b-thalassemia. Program and Abstracts of the 10 th
International Congress of Endocrinology, San Francisco; 1996. p. 1-127.
Soliman AT, elZalabany MM, Mazloum Y, Bedair SM, Ragab MS, Rogol AD, et al
. Spontaneous and provoked growth hormone (GH) secretion and insulin-like growth factor I (IGF-I) concentration in patients with beta thalassaemia and delayed growth. J Trop Pediatr 1999;45:327-37.
Blair JC, Camacho-Hübner C, Miraki Moud F, Rosberg S, Burren C, Lim S, et al
. Standard and low-dose IGF-I generation tests and spontaneous growth hormone secretion in children with idiopathic short stature. Clin Endocrinol (Oxf) 2004;60:163-8.
Werther GA, Mathews RN, Burger HG, Herrington AC. Lack of response of non-suppressible insulin-like activity in thalassemia major. J Clin Endocrinol Metab 1981;53:806-9.
Chrysis DC, Alexandrides TK, Koromantzou E, Georgopoulos N, Vassilakos P, Kiess W, et al
. Novel application of IGF-I and IGFBP-3 generation tests in the diagnosis of growth hormone axis disturbances in children with beta-thalassaemia. Clin Endocrinol (Oxf) 2001;54:253-9.
Soliman AT, Khalafallah H, Ashour R. Growth and factors affecting it in thalassemia major. Hemoglobin 2009;33:S116-26.
Karydis I, Karagiorga-Lagana M, Nounopoulos C, Tolis G. Basal and stimulated levels of growth hormone, insulin-like growth factor-I (IGF-I), IGF-I binding and IGF-binding proteins in beta-thalassemia major. J Pediatr Endocrinol Metab 2004;17:17-25.
Valenti S, Giusti M, McGuinness D, Guido R, Mori PG, Giordano G, et al
. Delayed puberty in males with beta-thalassemia major: Pulsatile gonadotropin-releasing hormone administration induces changes in gonadotropin isoform profiles and an increase in sex steroids. Eur J Endocrinol 1995;133:48-56.
Mauras N, Rogol AD, Haymond MW, Veldhuis JD. Sex steroids, growth hormone, insulin-like growth factor-1: Neuroendocrine and metabolic regulation in puberty. Horm Res 1996;45:74-80.
Soliman AT, elZalabany MM, Ragab M, Abdel Fattah M, Hassab H, Rogol AD, et al
. Spontaneous and GnRH-provoked gonadotropin secretion and testosterone response to human chorionic gonadotropin in adolescent boys with thalassaemia major and delayed puberty. J Trop Pediatr 2000;46:79-85.
Roth C, Pekrun A, Bartz M, Jarry H, Eber S, Lakomek M, et al
. Short stature and failure of pubertal development in thalassaemia major: Evidence for hypothalamic neurosecretory dysfunction of growth hormone secretion and defective pituitary gonadotropin secretion. Eur J Pediatr 1997;156:777-83.
Moayeri H, Oloomi Z. Prevalence of growth and puberty failure with respect to growth hormone and gonadotropins secretion in beta-thalassemia major. Arch Iran Med 2006;9:329-34.
Soliman AT, Nasr I, Thabet A, Rizk MM, El Matary W. Human chorionic gonadotropin therapy in adolescent boys with constitutional delayed puberty vs those with beta-thalassemia major. Metabolism 2005;54:15-23.
Veldhuis JD, Roemmich JN, Richmond EJ, Rogol AD, Lovejoy JC, Sheffield-Moore M, et al
. Endocrine control of body composition in infancy, childhood, and puberty. Endocr Rev 2005;26:114-46.
Mahachoklertwattana P, Yimsumruay T, Poomthavorn P, Chuansumrit A, Khlairit P. Acute effects of blood transfusion on growth hormone and insulin-like growth factor-1 levels in children with thalassemia. Horm Res Paediatr 2011;75:240-5.
Soliman AT, El-Matary W, Fattah MM, Nasr IS, El Alaily RK, Thabet MA. The effect of high-calorie diet on nutritional parameters of children with beta-thalassaemia major. Clin Nutr 2004;23:1153-8.
Abdulrazzaq YM, Ibrahim A, Al-Khayatb Al, Dawson K. Beta-thalassemia major and its effect on amino acid metabolism and growth in patients in the United Arab Emirates. Clin Chim Acta 2005;352:183-90.
Fuchs GJ, Tienboon P, Linpisarn S, Nimsakul S, Leelapat P, Tovanabutra S, et al
. Nutritional factors and thalassaemia major. Arch Dis Child 1996;74:224-7.
Soliman A, Adel A, Wagdy M, Al Ali M, ElMulla N. Calcium homeostasis in 40 adolescents with beta-thalassemia major: A case-control study of the effects of intramuscular injection of a megadose of cholecalciferol. Pediatr Endocrinol Rev 2008;6:149-54.
Soliman AT, Al Khalaf F, Alhemaidi N, Al Ali M, Al Zyoud M, Yakoot K. Linear growth in relation to the circulating concentrations of insulin-like growth factor I, parathyroid hormone, and 25-hydroxy vitamin D in children with nutritional rickets before and after treatment: Endocrine adaptation to vitamin D deficiency. Metabolism 2008;57:95-102.
Cranney A, Horsley T, O'Donnell S, Weiler H, Puil L, Ooi D, et al
. Effectiveness and safety of vitamin D in relation to bone health. Evid Rep Technol Assess (Full Rep) 2007;158:1-235.
Vogiatzi MG, Macklin EA, Trachtenberg FL, Fung EB, Cheung AM, Vichinsky E, et al
., Thalassemia Clinical Research Network. Differences in the prevalence of growth, endocrine and vitamin D abnormalities among the various thalassaemia syndromes in North America. Br J Haematol 2009;146:546-56.
Ameri P, Giusti A, Boschetti M, Murialdo G, Minuto F, Ferone D. Interactions between vitamin D and IGF-I: From physiology to clinical practice. Clin Endocrinol (Oxf) 2013;79:457-63.
Yazdideha MS, Faranosh M. Evaluation of serum zinc in children affected with betathalassemic patients. Res Med 2004;24:7-9.
Kajanachumpol S, Tatu T, Sasanakul W. Zinc and copper status of thalassemia children. Southeast Asian J Trop Med Public Health 1997;28:877-80.
Mahyar A. The preventive role of zinc from communicable and non communicable diseases in children. NCD Malaysia 2005;4:21-6.
Cesur Y, Yordaman N, Doðan M. Serum insulin-like growth factor-I and insulin-like growth factor binding protein-3 levels in children with zinc deficiency and the effect of zinc supplementation on these parameters. J Pediatr Endocrinol Metab 2009;22:1137-43.
Imamoðlu S, Bereket A, Turan S, Taga Y, Haklar G. Effect of zinc supplementation on growth hormone secretion, IGF-I, IGFBP-3, somatomedin generation, alkaline phosphatase, osteocalcin and growth in prepubertal children with idiopathic short stature. J Pediatr Endocrinol Metab 2005;18:69-74.
Arcasoy A, Canata D, Sinav B, Kutlay L, Oguz N, Sen M. Serum zinc levels and zinc binding capacity in thalassemia. J Trace Elem Med Biol 2001;15:85-7.
Arcasoy A, Çavdar AO, Cin S, Erten J, Babacan E, Gözdaþoðlu S, et al
. Effects of zinc Supplementation on linear growth in beta-thalassemia (a new approach). Am J Hematol 1987;24:127-36.
Kattamis C, Touliatos N, Haidas S, Matsaniotis N. Growth of children with thalassaemia: Effect of different transfusional regimens. Arch Dis Child 1970;45:502-9.
De Sanctis V, Katz M, Vullo C, Bagni B, Ughi M, Wonke B. Effect of different treatment regimes on linear growth and final height in beta-thalassaemia major. Clin Endocrinol (Oxf) 1994;40:791-8.
Hashemi A, Ghilian R, Golestan M, Akhavan Ghalibaf M, Zare Z, Dehghani MA. The study of growth in thalassemic patients and its correlation with serum ferritin level. Iran J Pediatr Hematol Oncol 2011;1:147-51.
Hamidah A, Arini MI, Zarina AL, Zulkifli SZ, Jamal R. Growth velocity in transfusion dependent prepubertal thalassemia patients: Results from a thalassemia center in Malaysia. Southeast Asian J Trop Med Public Health 2008;39:900-5.
Shalitin S, Carmi D, Weintrob N, Phillip M, Miskin H, Kornreich L, et al
. Serum ferritin level as a predictor of impaired growth and puberty in thalassemia major patients. Eur J Haematol 2005;74:93-100.
Pemde HK, Chandra J, Gupta D, Singh V, Sharma R, Dutta AK. Physical growth in children with transfusion-dependent thalassemia. Pediatr Health Med Ther 2011;2:13-9.
Conchillo M, Prieto J, Quiroga J. Insulin-like growth factor I (IGF-I) and liver cirrhosis. Rev Esp Enferm Dig 2007;99:156-64.
Wallek G, Friedrich N, Ittermann T, Mayerle J, Völzke H, Nauck M. IGF-1 and IGFBP-3 in patients with liver disease/IGF-1 und IGFBP-3 bei Patienten mit Lebererkrankungen. Laboratoriumsmedizin 2013;37:13-20.
Soliman A, Al Yafei F, Al-Naimi L, Almarri N, Sabt A, Yassin M, et al
. Study on linear growth and thyroid function for 12 years in patients with β thalassemia major. Endocrine 2013;32:992.
Soliman AT, De Sanctis V, Bedair EM. Congenital hypothyroidism: Effects on linear growth, catch- up growth, gh-igf-i axis and bones. In: Potluková E, editor. Current Topics in Hypothyroidism with Focus on Development.
Sanctis V, Soliman A, Campisi S, Yassin M. Thyroid disorders in thalassaemia: An update. Curr Trends Endocrinol 2012;6:17-27.
Multicenter study of prevalence of endocrine complications in thalassaemia major. Italian Working Group On Endocrine Complications in Non-Endocrine Diseases. Clin Endocrinol (Oxf) 1994;42:581-6.
Zandian KM, Mohammadian Nasab AM, Riahy K, Shahbazian H, Dehder KF, Ashrafi MR, et al
. The prevalence of hypoparathyroidism among patients with major thalassemia aged above 10 years. Iran J Pediatr 2005;15:157-64.
Lombardi G, Di Somma C, Vuolo L, Guerra E, Scarano E, Colao A. Role of IGF-I on PTH effects on bone. J Endocrinol Invest 2010;33:22-6.
McCarthy TL, Centrella M, Canalis E. Regulatory effects of insulin-like growth factors I and II on bone collagen synthesis in rat calvarial cultures. Endocrinology 1989;124:301-9.
Mochizuki H, Hakeda Y, Wakatsuki N, Usui N, Akashi S, Sato T, et al
. Insulin like growth factor-I supports formation and activation of osteoclasts. Endocrinology 1992;131:1075-80.
Scacchi M, Danesi L, Cattaneo, Valassi E, Pecori Giraldi F, Argento C, et al
. Bone demineralization in adult thalassaemic patients: Contribution of GH and IGF-I at different skeletal sites. Clin Endocrinol (Oxf) 2008;69:202-7.
Soliman AT, El Banna N, Abdel Fattah M, ElZalabani MM, Ansari BM. Bone mineral density in prepubertal children with beta-thalassemia: Correlation with growth and hormonal data. Metabolism 1998;47:541-8.
Bayraktaroðlu S, Aydinok Y, Yildiz D, Uluer H, Savaþ R, Alper H. The relationship between the myocardial T2* value and left ventricular volumetric and functional parameters in thalassemia major patients. Diagn Interv Radiol 2011;17:346-51.
Aessopos A, Farmakis D, Hatziliami A, Fragodimitri C, Karabatsos F, Joussef J, et al
. Cardiac status in well-treated patients with thalassemia major. Eur J Haematol 2004;73:359-66.
Bisi G, Podio V, Valetto MR, Broglio F, Bertuccio G, DEl Rio G, et al
. Radionuclide angiocardiographic evaluation of the cardiovascular effects of recombinant human IGF-I in normal adults. Eur J Endocrinol 1999;140:322-7.
|This article has been cited by|
||Growth hormone therapy for people with thalassaemia
| ||Chin Fang Ngim,Nai Ming Lai,Janet YH Hong,Shir Ley Tan,Amutha Ramadas,Premala Muthukumarasamy,Meow-Keong Thong |
| ||Cochrane Database of Systematic Reviews. 2020; |
|[Pubmed] | [DOI]|
||A Perception on Genome-Wide Genetic Analysis of Metabolic Traits in Arab Populations
| ||Prashantha Hebbar,Jehad Ahmed Abubaker,Mohamed Abu-Farha,Jaakko Tuomilehto,Fahd Al-Mulla,Thangavel Alphonse Thanaraj |
| ||Frontiers in Endocrinology. 2019; 10 |
|[Pubmed] | [DOI]|
||Growth hormone therapy for people with thalassaemia
| ||Chin Fang Ngim,Nai Ming Lai,Janet YH Hong,Shir Ley Tan,Amutha Ramadas,Premala Muthukumarasamy,Meow-Keong Thong |
| ||Cochrane Database of Systematic Reviews. 2017; |
|[Pubmed] | [DOI]|
||Growth and endocrine issues in children with thalassemia
| ||Preeti Singh,Anju Seth |
| ||Pediatric Hematology Oncology Journal. 2017; |
|[Pubmed] | [DOI]|
||Sickle cell/ß-thalassemia: Comparison of Sß0and Sß+Brazilian patients followed at a single institution
| ||Bruno Deltreggia Benites,Stephany Oliveira Bastos,Gabriel Baldanzi,Allan de Oliveira dos Santos,Celso Dario Ramos,Fernando Ferreira Costa,Simone Cristina Olenscki Gilli,Sara Teresinha Olalla Saad |
| ||Hematology. 2016; : 1 |
|[Pubmed] | [DOI]|
||Current growth patterns in children and adolescents with thalassemia major
| ||Raffaella Origa,Fabrice Danjou,Valeria Orecchia,Antonietta Zappu,Carlo Dessì,Maria Loreta Foschini,Giovan Battista Leoni,Paolo Moi,Maddalena Morittu,Anna Demurtas,Sandro Loche |
| ||Blood. 2016; 128(21): 2580 |
|[Pubmed] | [DOI]|