Studies on the Possible Mechanism for Deficiency of Nonsuppressible Insulin-Like Activity in Thalassemia Major*

Herington, Adrian C.; Werther, G; Matthews, R. N.; Burger, Henry

doi:10.1210/jcem-52-3-393

Cited by 46 publications

(18 citation statements)

References 29 publications

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“…On the other hand, some authors did not find a depres sion of hepatic protein synthesis in thalassemic patients and suggest that the low serum somatomedin activity could be due to some other mechanisms rather than a gen eral liver impairment [30,34], These authors reported a specific iron-inhibitory effect on somatomedin synthesis as well as an increase in degradation rate [30].…”

Section: Discussionmentioning

confidence: 97%

GH Secretion in Thalassemic Patients with Short Stature

Luca

Maggiolini²,

Bria³

et al. 1995

Horm Res

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The physiological role of GH secretion on growth retardation remains to be elucidated especially in patients with β-thalassemia. In the present study, we investigated IGF-1 circulating levels as well as GH release following GHRH alone or combined with some inhibitors of somatostatin: pyridostigmine and arginine. In thalassemic patients lower IGF-1 circulating levels appear to be negatively correlated with both aspartate aminotransferase and alanine aminotransferase as well as with ferritin circulating levels indicating a probable role of hepatic hemosiderosis in IGF-1 production. The authors however suggest that reduced IGF-1 secretion is not the main cause of growth retardation since this would have elicited an enhanced response of GHRH in the presence of a normal hypothalamic pituitary axis. In contrast, they noticed that GH response to GHRH when expressed as area under the curve was lower in thalassemic patients compared to controls. The combination of GHRH with either pyridostigmine or arginine induced a GH secretion in thalassemics which was comparable to that of controls. The results of this study lead to conclude that the alteration of GH secretion is due, in such patients, to an increased somatostatin activity.

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Section: Discussionmentioning

confidence: 97%

GH Secretion in Thalassemic Patients with Short Stature

Luca

Maggiolini²,

Bria³

et al. 1995

Horm Res

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“…In a recent cross-sectional survey of growth and sexual maturation among Chinese children with /?-thalassaemia major, growth retardation was found in 75% of the girls and 62% of the boys over 12 years of age with lack of sexual development in 50% of the boys and 37.5% of the girls (Kwan et al, 1995). In the adolescent thalassaemic patients, GH deficiency is rare but subnormal IGF-I levels have been reported in a significant proportion (Saenger et af., 1980;Herington et af., 1981;Werther et al, 1981). The low serum IGF-I levels, which fail to rise following exogenous GH, and the presence of normal GH reserve in these patients is suggestive of GH resistance (Werther et al, 1981).…”

mentioning

confidence: 95%

“…In the adolescent thalassaemic patients, GH deficiency is rare but subnormal IGF-I levels have been reported in a significant proportion (Saenger et af., 1980;Herington et af., 1981;Werther et al, 1981). The low serum IGF-I levels, which fail to rise following exogenous GH, and the presence of normal GH reserve in these patients is suggestive of GH resistance (Werther et al, 1981). A significant though modest improvement in growth response to G H has been reported in 8 short thalassaemic children with impaired GH 359 0 1995 Blackwell Science Ltd secretion (Scacchi et al, 1991).…”

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confidence: 97%

Growth hormone treatment of short Chinese children with β‐thalassaemia major without GH deficiency

Low

Kwan

Lim

et al. 1995

Clinical Endocrinology

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SummaryOBJECTIVE Desplte regular transfuslon and desferrioxamine treatment, growth fallure Is commonly seen In adolescent children wlth Pthalassaemla malor. The growth failure has been thought to be due to GH reslstance rather than GH deflclency. We Investigated the effect of GH on short non-GH deflclent chlldren wlth P thalassaemla. DESIGN Recomblnant human GH was given In a dose of 0.14 IUlkglday subcutaneously in an open study.PATIENTS Flfteen prepubertal Chlnese children with p thalassaemla malor (ranglng from 7.16 to 147 years In age) wlth height -1.5 SD or more below the population mean for age and a growth velocity of less than 5 cmlyear were treated with growth hormone for one year. All chlldren had peak GH response >lSmlU/I to lnsulln induced hypoglycaemla and normal thyroid functlon and adrenal reserve. MEASUREMENTS Anthropometric measurements were performed every 3 months. Morning urine was tested twlce weekly for glycosurla. Blood count, renal and liver function tests, fastlng blood glucose, IGF-l and fructosamine levels were assessed at entry and every 3 months during treatment. Fasting lnsulln was measured before and after 3 and 12 months of GH treatment. Skeletal maturlty was assessed before and after one year of treatment. RESULTS Treatment was stopped in two chlldren after 6 months because of poor growth response and noncompliance wlth treatment and In one child at 9 months because o f bone marrow transplantation. In the 13 chlldren, the growth velocity Increased from 3.6 * 0.7 cmlyear to

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“…Endocrine studies in these patients have frequently but not always revealed the presence of normal thyroid function, and normal GH response to provocative stimuli (2)(3)(4)(5)(6)(7)(8)(9)). An adequate endocrine explanation for the short stature recently was provided with the demonstration of marked reduction of •somatomedin activity (10,11). The underlying defect in these patients seems to be an impaired human (h) GHreceptor interaction or a postreceptor defect, both of which would lead to impairment of GH-induced generation of somatomedin (10,11).…”

mentioning

confidence: 99%

“…An adequate endocrine explanation for the short stature recently was provided with the demonstration of marked reduction of •somatomedin activity (10,11). The underlying defect in these patients seems to be an impaired human (h) GHreceptor interaction or a postreceptor defect, both of which would lead to impairment of GH-induced generation of somatomedin (10,11). In a recent study, a 3-day course of exogenous hGH failed to cause the expected rise of somatomedin(s) in a group of children with thalassemia major (12).…”

mentioning

confidence: 99%

Impaired Growth Hormone (GH) Response to GHReleasing Hormone in Thalassemia Major*

Pintor

Cella

Manso

et al. 1986

The Journal of Clinical Endocrinology & Metabolism

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The response of GH to acute administration of GH-releasing hormone (GHRH) was evaluated in 19 patients with thalassemia major and 8 normal children. In 13 of the 19 patients, GHRH induced a definite increase (greater than 5 ng/ml) in plasma GH levels, with peaks occurring 5-45 min postinjection. In 6 patients there was little or no GH rise after GHRH treatment. Overall, the mean GH response to GHRH of patients with thalassemia was lower than that of normal children. These data indicate that in thalassemia major, in addition to the described defect at the hepatic GH receptor or postreceptor level which impedes generation of somatomedins, there may be a marked impairment in somatotroph function. In one patient in whom the GH response to GHRH was superimposable on that of normal subjects, there was a blunted GH response to insulin hypoglycemia. This finding indicates that functional damage in hypothalamic structures for GH control can also occur in thalassemic patients.

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Studies on the Possible Mechanism for Deficiency of Nonsuppressible Insulin-Like Activity in Thalassemia Major*

Cited by 46 publications

References 29 publications

GH Secretion in Thalassemic Patients with Short Stature

GH Secretion in Thalassemic Patients with Short Stature

Growth hormone treatment of short Chinese children with β‐thalassaemia major without GH deficiency

Impaired Growth Hormone (GH) Response to GHReleasing Hormone in Thalassemia Major*

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