Acquired Growth Hormone Resistance in Patients with Hypercatabolism

Bentham, J.; Rodriguez-Arnao, J.; Ross, R. J. M.

doi:10.1159/000183772

Cited by 94 publications

(32 citation statements)

References 20 publications

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“…This is probably brought about by the effects of cytokines such as tumor necrosis factor-a (TNF-a), interleukin-1 (IL-1) and interleukin-6 (IL-6). It has been hypothesized ± though it remains unproved ± that reduced GH-receptor expression and thus low circulating IGF-I levels are the primary events (cytokine-induced) which in turn ± through reduced negative feedback inhibition ± drives the abundant release of GH during acute stress, exerting direct lipolytic, insulin-antagonizing and immune-stimulatory actions, while the indirect IGF-I-mediated somatotropic effects are attenuated (20,21). This phenomenon would make a lot of sense in stressful conditions.…”

Section: Changes In the Acute Phase Of Critical Illnessmentioning

confidence: 99%

Novel insights into the neuroendocrinology of critical illness

Berghe

2000

European Journal of Endocrinology

226

104

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An unexplained hallmark of prolonged critical illness is the fact that food does not prevent or reverse protein wasting, while fat is paradoxically accrued. This`wasting syndrome' often persists after the underlying disease has been resolved and thus perpetuates intensive care dependency. Although the crucial role of an intact hypothalamus±pituitary axis for homeostasis during stress is well recognized, the differences between the neuroendocrine changes observed in acute and prolonged critical illness were only recently described. Novel insights in this area are reviewed here.The initial endocrine stress response consists primarily of a peripheral inactivation of anabolic pathways while pituitary activity is essentially ampli®ed or maintained. These responses presumably provide the metabolic substrates and host defense required for survival and to delay anabolism, and thus should be considered as adaptive and bene®cial. Persistence of this acute stress response throughout the course of critical illness was hitherto assumed. This assumption has now been invalidated, since a uniformly reduced pulsatile secretion of ACTH, TSH, LH, prolactin (PRL) and GH has been observed in protracted critical illness, causing diminished stimulation of several target organs. Impaired pulsatile secretion of anterior pituitary hormones in the chronic phase of critical illness seems to have a hypothalamic rather than a pituitary origin, as administration of relevant releasing factors evoked immediate and pronounced pituitary hormone release. A reduced availability of TRH, one of the endogenous ligands of the GH-releasing peptide (GHRP) receptor (such as the recently discovered ghrelin) and, in very long-stay critically ill men, also of GHRH, appear to be involved. This hypothesis was further explored by investigating the effects of continuous i.v. infusion of GHRH, GHRP, TRH and their combinations for several days. Pulsatile secretion of GH, TSH and PRL was re-ampli®ed by relevant combinations of releasing factors which also substantially increased circulating levels of IGF-I, GH-dependent binding proteins, thyroxine and tri-iodothyronine (T3) while avoiding a rise in reverse T3. Active feedback-inhibition loops prevented overstimulation of target organs and metabolic improvement was noted with the combined infusion of GHRP and TRH. Whether this novel endocrine strategy will also enhance clinical recovery from critical illness remains to be explored.

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Section: Changes In the Acute Phase Of Critical Illnessmentioning

confidence: 99%

Novel insights into the neuroendocrinology of critical illness

Berghe

2000

European Journal of Endocrinology

226

104

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“…Nevertheless, recombinant human GH (rhGH) administration to children with JCA partially counteracts the adverse effects of this disease on growth and metabolism (Davies et al 1994, Touati et al 1998. GH and IGF-I are essential hormones in stimulating protein synthesis and body weight, and abnormalities in the IGF-I and IGFBPs have been associated with catabolic states (Bentham et al 1993). These data indicate that the wasting syndrome observed in adjuvant-induced arthritis (Roubenoff et al 1997) can be, in part, secondary to the alterations in GH, IGF-I and IGFBPs.…”

Section: Introductionmentioning

confidence: 99%

IGF-I and IGF-I-binding proteins in rats with adjuvant-induced arthritis given recombinant human growth hormone

Cáceres¹,

Villanúa²,

Soto³

et al. 2000

Journal of Endocrinology

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Adjuvant-induced arthritis in rats is associated with growth failure, hypermetabolism and accelerated protein breakdown. We have previously reported that adjuvant-induced arthritis in rats results in a decrease in body weight gain, pituitary GH mRNA, circulating GH and IGF-I together with an increase in serum IGF-binding proteins (IGFBPs). The aim of this study was to analyze the role of GH in the decrease in body weight and in the alterations in the IGF-I system observed in chronic inflammation.Male Wistar rats were injected with complete Freund's adjuvant and 16 days later arthritic rats were injected daily with recombinant human GH (rhGH) (3 IU/kg s.c.) for 8 days; control rats received 250 µl saline. Arthritis significantly decreased body weight gain and serum IGF-I. These decreases were not due to the reduced food intake, since in pair-fed rats they were not observed. Furthermore, administration of rhGH to arthritic rats increased body weight gain without modifying food intake. To further investigate the effect of GH administration, 14 days after adjuvant injection both control and arthritic rats were treated with 0, 1·5, 3 or 6 IU/kg of rhGH. GH treatment at the dose of 3 and 6 IU/kg significantly increased body weight gain in arthritic rats. GH administration, at the higher dose of 6 IU/kg, increased hepatic and serum concentrations of IGF-I in both control and arthritic rats. In control rats, rhGH at the three doses assayed increased circulating IGFBP-3. GH treatment in arthritic rats decreased IGFBP-1 and -2, and did not modify IGFBP-4. GH treatment at the dose of 3 IU/kg also decreased circulating IGFBP-3 in arthritic rats.These data suggest that GH treatment can ameliorate the catabolism observed in adjuvant-induced arthritis, an effect mediated, at least in part, by modifications in the circulating IGFBPs.

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“…Furthermore, collecting the blood sample for the IGF-1 measurement is easier, because it does not require resting, and serum IGF-1 level shows no diurnal variation. Serum IGF-1 levels, however, have variations for age and gender, and are suppressed in some diseases and conditions including diabetes mellitus with poorly controlled glycemia (Ross et al 1991;Bentham et al 1993;Lim et al 2007).…”

mentioning

confidence: 99%

Acromegaly with Normal IGF-1 Levels Probably due to Poorly Controlled Diabetes Mellitus

Arihara

Sakurai

Yamada

et al. 2008

Tohoku J. Exp. Med.

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Acromegaly is characterized by the somatic disfigurement and excessive production of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Here we report a patient with aromegaly and diabetes mellitus, who showed normal IGF-1 levels in spite of elevated GH levels. The patient was a 52-year-old woman with acromegalic manifestations. Serum GH level was elevated (32.4 ng/mL) with hyperglycemia (fasting plasma glucose, 277 mg/dL) and an extremely high level of glycosylated hemoglobin (HbA1c 17.7%), whereas serum IGF-1 level was within normal range (110 ng/mL, normal range 37-266). Brain magnetic resonance imaging detected a pituitary tumor, with involvement of the right cavernous sinus. Oral glucose tolerance test (OGTT) showed no suppression of serum GH. Thyrotropin-releasing hormone test showed paradoxical increases in serum GH. We therefore diagnosed acromegaly accompanied with diabetes mellitus. A large amount of insulin (34 units/day) was required to control the blood glucose level. The patient was treated with octreotide, a somatostatin analogue, followed by transsphenoidal surgery. After the surgery, serum GH levels were suppressed by OGTT, although basal serum GH levels remained to be high. Basal serum GH levels, however, were normalized 5 months later. Blood glucose became well controlled by the diet alone. In contrast, serum IGF-1 increased to the range of 219-233 ng/mL. Pre-operative serum IGF-1 levels were low probably due to poorly controlled diabetes mellitus. In conclusion, the presence of normal serum IGF-1 levels cannot exclude the diagnosis of acromegaly especially when the patient is accompanied by diabetes mellitus.Acromegaly; Insulin-like Growth Factor-1 (IGF-1); Growth Hormone (GH); octreotide; transsphenoidal surgery. Tohoku

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Acquired Growth Hormone Resistance in Patients with Hypercatabolism

Cited by 94 publications

References 20 publications

Novel insights into the neuroendocrinology of critical illness

Novel insights into the neuroendocrinology of critical illness

IGF-I and IGF-I-binding proteins in rats with adjuvant-induced arthritis given recombinant human growth hormone

Acromegaly with Normal IGF-1 Levels Probably due to Poorly Controlled Diabetes Mellitus

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