Hexarelin as a test of pituitary reserve in patients with pituitary disease

Korbonits, Márta; Kaltsas, Gregory; Perry, Leslie; Grossman, Ashley; Monson, John P.; Besser, G. M.; Trainer, Peter J

doi:10.1046/j.1365-2265.1999.00828.x

Cited by 23 publications

(15 citation statements)

References 28 publications

(31 reference statements)

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“…The positive correlation between the extent of the ghrelin-elicited GH increase and the basal IGF-I concentrations in acromegalic patients suggests that GHSs are useful tools in assessing GH secretory capacity in both normal and pathological conditions, in agreement with previous findings in healthy subjects after hexarelin administration (19). Both ghrelin and hexarelin are able to stimulate ACTH and cortisol release in healthy subjects (6), even if hexarelin is not a useful test of ACTH/cortisol reserve in patients with pituitary diseases (19). Although the ACTH response to ghrelin in acromegalic patients was similar to control subjects, it is noteworthy that the cortisol response did not reach statistical significance.…”

Section: Discussionsupporting

confidence: 90%

“…GHS receptor expression is very high in GH-producing adenomas (16) and hexarelin, a synthetic GHS, possesses GH-and PRL-releasing activity in acromegalic patients (17,18). The positive correlation between the extent of the ghrelin-elicited GH increase and the basal IGF-I concentrations in acromegalic patients suggests that GHSs are useful tools in assessing GH secretory capacity in both normal and pathological conditions, in agreement with previous findings in healthy subjects after hexarelin administration (19). Both ghrelin and hexarelin are able to stimulate ACTH and cortisol release in healthy subjects (6), even if hexarelin is not a useful test of ACTH/cortisol reserve in patients with pituitary diseases (19).…”

Section: Discussionsupporting

confidence: 80%

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Ghrelin administration affects circulating pituitary and gastro-entero-pancreatic hormones in acromegaly

Arosio¹,

Ronchi²,

Gebbia³

et al. 2004

European Journal of Endocrinology

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Objective: Ghrelin, a gut -brain peptide involved in the control of energy homeostasis, affects anteropituitary and gastro-entero-pancreatic (GEP) hormone secretion in healthy subjects. We aimed to verify whether such hormonal responses are retained in acromegaly, a disease characterized by high GH, subnormal ghrelin and abnormal GEP hormone levels. Design and methods: The effect of ghrelin (3.3 mg/kg given after overnight fasting as an i.v. bolus) on GH, prolactin (PRL), adrenocorticotropin (ACTH), cortisol, insulin, glucose, total somatostatin (SS) and pancreatic polypeptide (PP) circulating levels were evaluated in seven non-diabetic patients with newly diagnosed acromegaly and in nine healthy controls. Results: Ghrelin elicited a prompt, marked increase of serum GH and PRL levels in all normal (from 1.6^0.6 to 52.9^7.8 and from 9.7^0.8 to 24.2^4.8 mg/l (means^S.E.M.), respectively) and acromegalic subjects (from 11.2^4.9 to 91.6^21.0 and from 42.9^26.1 to 113.8^79.0 mg/l, respectively). Both plasma ACTH and serum cortisol levels rose significantly in the controls, whereas the cortisol response was blunted in the acromegalic patients. Glucose levels rose earlier and insulin levels fell later in all subjects, with a significantly greater net insulin decrease in acromegalic than in healthy subjects (2 80^21 vs 2 17^4 pmol/l, P , 0.01). A prompt PP rise and a biphasic SS response occurred in all controls, whereas in the acromegalic group the PP response (from 26.1^5.0 to 92.2^39.0 pmol/l) and the SS response (from 11.9^3.0 to 19.7^4.0 ng/l) were quite variable. Conclusions: Ghrelin affects both pituitary and GEP hormones in acromegalic patients as in normal subjects. These findings suggest that ghrelin actions on the energy balance are mediated by complex interactive endocrine loops that involve also the gut and pancreas.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 80%

Ghrelin administration affects circulating pituitary and gastro-entero-pancreatic hormones in acromegaly

Arosio¹,

Ronchi²,

Gebbia³

et al. 2004

European Journal of Endocrinology

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“…The only other study of a single GHS test for diagnosis of GH deficiency in adults was performed by Korbonits et al (8). These authors used a different GHS (Hexarelin, 2 mg/kg) to investigate the GH response in 19 patients with possible pituitary disease.…”

Section: Discussionmentioning

confidence: 99%

Diagnosis of growth hormone deficiency in adults by testing with GHRP-6 alone or in combination with GHRH: comparison with the insulin tolerance test

Petersenn

Jung²,

Beil³

2002

European Journal of Endocrinology

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Objective: The diagnosis of GH deficiency in adults should be made using provocative testing of GH secretion. The insulin tolerance test (ITT) is recommended as the gold standard investigation. Because of the risk of serious complications, patients with epilepsy or known ischemic heart disease should not undergo this test. GHRP-6 is a synthetic hexapeptide that releases GH by binding to specific hypothalamic and pituitary receptors. We assessed the diagnostic capability of GH stimulation by GHRP-6 alone or in combination with GHRH in comparison to the results of an ITT. Design: Twenty patients underwent an ITT for suspected pituitary or adrenal disease. Either GHRP-6 (1 mg/kg) alone, or GHRP-6 in combination with GHRH (1 mg/kg) were administered on different days. Blood samples were obtained during a subsequent 90-min period for measurement of GH. Results: Ten patients had a GH peak response of less than 3 mg/l during ITT and were considered growth hormone deficient (GHD). The GH mean peak (^S.E.M., range) in this group was 0.7 mg/l (^0.3, 0.1 -2.9) compared with 14.5 mg/l (^3.5, 3.8 -40.8) in the group of patients with a GH peak response of more than 3 mg/l (growth hormone sufficient (GS)). For the GHRP-6 test, the GH mean peak was 1.3 mg/l (^0.6, 0.1 -6.7) in the GHD group versus 25.7 mg/l (^5.5, 7.7-54.2) in the GS group. After GHRP-6 þ GHRH, the GH mean peaks were 4.0 mg/l (^1.3, 0.2 -11.9) versus 54.7 mg/l (^11.1, 13.9 -136.0) respectively. During administration of GHRP-6, the only side effects observed were flush symptoms. Conclusions: Peak GH levels below 7 mg/l for the GHRP-6 test and below 13 mg/l for the combined GHRP-6 þ GHRH test identified all patients with GH deficiency correctly as defined by ITT. The results suggest that testing with GHRP-6 or GHRP-6 þ GHRH is as sensitive and specific as an ITT for the diagnosis of adult GH deficiency.

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“…This minor modification was beneficial, making hexarelin more stable and longer acting in vivo [63]. Hexarelin is more potent than GHRP-6 as a GH releaser [64][65][66].…”

Section: Growth Hormone Secretagogues (Ghs)mentioning

confidence: 99%

Implications of ghrelin and hexarelin in diabetes and diabetes-associated heart diseases

et al. 2015

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Ghrelin and its synthetic analog hexarelin are specific ligands of growth hormone secretagogue (GHS) receptor. GHS have strong growth hormone-releasing effect and other neuroendocrine activities such as stimulatory effects on prolactin and adrenocorticotropic hormone secretion. Recently, several studies have reported other beneficial functions of GHS that are independent of GH. Ghrelin and hexarelin, for examples, have been shown to exert GH-independent cardiovascular activity. Hexarelin has been reported to regulate peroxisome proliferator-activated receptor gamma (PPAR-γ) in macrophages and adipocytes. PPAR-γ is an important regulator of adipogenesis, lipid metabolism, and insulin sensitization. Ghrelin also shows protective effects on beta cells against lipotoxicity through activation of phosphatidylinositol-3 kinase/protein kinase B, c-Jun N-terminal kinase ( JNK) inhibition, and nuclear exclusion of forkhead box protein O1. Acylated ghrelin (AG) and unacylated ghrelin (UAG) administration reduces glucose levels and increases insulinproducing beta cell number, and insulin secretion in pancreatectomized rats and in newborn rats treated with streptozotocin, suggesting a possible role of GHS in pancreatic regeneration. Therefore, the discovery of GHS has opened many new perspectives in endocrine, metabolic, and cardiovascular research areas, suggesting the possible therapeutic application in diabetes and diabetic complications especially diabetic cardiomyopathy. Here, we review the physiological roles of ghrelin and hexarelin in the protection and regeneration of beta cells and their roles in the regulation of insulin release, glucose, and fat metabolism and present their potential therapeutic effects in the treatment of diabetes and diabetic-associated heart diseases. Disciplines Medicine and Health Sciences Publication DetailsMosa, R., Zhang, Z., Shao, R., Deng, C., Chen, J. & Chen, C. (2015). Implications of ghrelin and hexarelin in diabetes and diabetes-associated heart diseases. Endocrine, 49 (2) AbstractGhrelin and its synthetic analog hexarelin are specific ligands of growth hormone secretagogue (GHS) receptor. GHS have strong growth hormone-releasing effect and other neuroendocrine activities such as stimulatory effects on prolactin and adrenocorticotropic hormone secretion. Recently, several studies have reported other beneficial functions of GHS that are independent of GH. Ghrelin and hexarelin, for examples, have been shown to exert GH-independent cardiovascular activity. Hexarelin has been reported to regulate peroxisome proliferator-activated receptor gamma (PPAR-γ) in macrophages and adipocytes. PPAR-γ is an important regulator of adipogenesis, lipid metabolism, and insulin sensitization. Ghrelin also shows protective effects on beta cells against lipotoxicity through activation of phosphatidylinositol-3 kinase/protein kinase B, c-Jun N-terminal kinase (JNK) inhibition, and nuclear exclusion of forkhead box protein O1. Acylated ghrelin (AG) and unacylated ghrelin (UAG) administration redu...

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Hexarelin as a test of pituitary reserve in patients with pituitary disease

Cited by 23 publications

References 28 publications

Ghrelin administration affects circulating pituitary and gastro-entero-pancreatic hormones in acromegaly

Ghrelin administration affects circulating pituitary and gastro-entero-pancreatic hormones in acromegaly

Diagnosis of growth hormone deficiency in adults by testing with GHRP-6 alone or in combination with GHRH: comparison with the insulin tolerance test

Implications of ghrelin and hexarelin in diabetes and diabetes-associated heart diseases

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