Somatostatin Infusion Withdrawal: Studies in Normal Children and in Children with Growth Hormone Deficiency

Cappa, Marco; Rigamonti, Antonello E.; Bizzarri, Carla; Porzio, Ottavia; Civolani, Patrizia; Cella, Silvano G.; Loche, Sandro; Müller, Eugenio E.

doi:10.1210/jcem.84.12.6282

Cited by 13 publications

(10 citation statements)

References 37 publications

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“…Thus, SS infusion withdrawal (SSIW) may represent a test to probe, inferentially, endogenous GHRH function, and may provide a potential tool in the diagnosis of growth disorders due to GH hyposecretory states (30) or to assess the declining GHRH function in ageing (29).…”

Section: Introductionmentioning

confidence: 99%

Growth hormone (GH) rebound rise following somatostatin infusion withdrawal: studies in dogs with the use of GH-releasing hormone and a GH-releasing peptide

Rigamonti

Cavallera

Bonomo³

et al. 2001

European Journal of Endocrinology

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Objective: Evidence has been presented that in both animals and humans the rebound secretion of growth hormone (GH) following withdrawal of an infusion of somatostatin (SS) is due to the functional activation of the hypothalamic GH-releasing hormone (GHRH) neurons of the recipient organism. Based on this premise, this study has sought to assess the existence of functional interactions between endogenous GHRH released by a SS infusion withdrawal (SSIW) and growth hormone-releasing peptides (GHRPs), a class of compounds allegedly acting via GHRH. Methods: Five young dogs (3 to 4 years old, 2 male and 3 female) were administered, on different occasions, three consecutive intravenous boli of physiological saline (0.1 ml/kg), or GHRH (2 mg/kg), or EP92632 (125 mg/kg), a GHRP compound, or GHRH plus EP92632 at the end of three cycles of 1-h SS infusions (8 mg/(kgÂh)) or during a 6-h infusion of saline. Results: Under saline infusion (SALI), plasma GH levels were unaltered, whereas each SSIW cycle was followed by similar GH secretory episodes. Administration of the ®rst GHRH bolus under SALI induced a rise in plasma GH concentrations slightly higher than that induced by the ®rst cycle of SSIW, but the GH response to the second and third GHRH boli was similar to that after SSIW. Following SSIW, the response to the ®rst bolus of GHRH was higher than that during SALI, but the second and third cycles of SSIW induced GH responses similar to those evoked by the GHRH bolus. During SALI, administration of the ®rst bolus of EP92632 induced a rise in plasma GH which was higher than that induced by the ®rst GHRH bolus, the second bolus elicited a GH peak of lesser amplitude and there was a partial restoration of the GH response to the third peptide bolus. SSIW strikingly enhanced the GH release to the ®rst EP92632 bolus, a pattern also present, although to a lesser extent, with the second and third cycles of SSIW. Under SALI, combined administration of GHRH and EP92632 had a synergistic effect on GH release, but a progressive reduction was present in the GH response to the second and third GHRH plus EP92632 boli. SSIW increased only weakly the GH response to the ®rst co-administration of the peptides over that present after administration of EP92632 alone, and did not induce a GH response higher than that present during SALI when the second bolus of the peptides was administered; after the third SSIW a GH rise higher than that present during SALI was elicited by the combined administration of the peptides. Conclusions: (i) the uniformity of the GH rebound responses to multiple cycles of SSIW may indicate that the latter activate a physiological mechanism which mimics that normally controlling GH pulse generation; (ii) EP92632 elicits, under our experimental conditions, a plasma GH rise higher than that induced by GHRH; (iii) SSIW enhances the GH response to EP92639 alone, to an extent reminiscent of that following combined administration of GHRH and EP92632. This pattern reinforces the view that SSIW elicits release of end...

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Section: Introductionmentioning

confidence: 99%

Growth hormone (GH) rebound rise following somatostatin infusion withdrawal: studies in dogs with the use of GH-releasing hormone and a GH-releasing peptide

Rigamonti

Cavallera

Bonomo³

et al. 2001

European Journal of Endocrinology

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“…The degree of rebound GH secretion after cessation of a SS infusion in the experimental animal is dependent on endogenous GHRH, as verified by GHRH immunoneutralization experiments, and direct measurement of GHRH in pituitary venous blood (35,36). Accordingly, post-SS rebound GH secretion has been used as a surrogate of hypothalamic GHRH release and action (24,26). Thus, our data are consistent with the hypothesis that low levels of endogenous estrogens regulate GHRH release and/or action in healthy postmenopausal women.…”

Section: Discussionmentioning

confidence: 99%

Endogenous Estrogen Regulates Somatostatin-Induced Rebound GH Secretion in Postmenopausal Women

Veldhuis

Erickson

Yang

et al. 2016

The Journal of Clinical Endocrinology &Amp; Metabolism

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Background: Systemic concentrations of T, estradiol (E2), GH, IGF-1, and IGF binding protein-3 decline in healthy aging individuals. Conversely, T and E2 stimulate GH and IGF-1 production in hypogonadal patients. Hypothesis: Because E2 stimulates GH secretion, putatively via the nuclear estrogen receptor-α and E2 and GH fall with menopause, we postulated that diminished endogenous E2 contributes to low GH output in older women. Location: The study was conducted at the Mayo Center for Clinical and Translational Science. Study Design: This was a randomized, double-blind, controlled study in 60 healthy postmenopausal women treated with the following: 1) double placebo; 2) anastrozole, a potent inhibitor of aromatase-enzyme activity, which mediates E2 synthesis from T; and/or 3) fulvestrant, a selective estrogen receptor-α antagonist. Methods: GH pulse generation was quantified by frequent GH sampling before and after short-term iv somatostatin infusion, thought to induce hypothalamic GHRH-mediated rebound-like GH secretion. Results: On anastrozole, E2 fell from 3.1 ± 0.35 pg/mL to 0.36 ± 0.04 pg/mL, and estrone from 13 ± 1.4 pg/mL to 1.9 ± 0.01 pg/mL (P < .001) by mass spectrometry. Estrogen values were unchanged by fulvestrant. T concentrations did not change. One-hour peak GH rebound after somatostatin infusion declined markedly during both estrogen-deprivation schedules (P < .001). Mean (150 min) maximal GH rebound decreased comparably (P < .001). Measures of GH rebound correlated negatively with computed tomography-estimated abdominal visceral fat (all P < .05). Conclusion: These data suggest a previously unrecognized dependence of hypothalamo-pituitary GH regulation on low levels of endogenous estrogen after menopause.

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“…GHRH hyposecretion, possibly associated with an enhanced SS function and pituitary impairment, would indicate the OB state. Further studies will allow a better understanding of the hypothalamic events triggered by SSIW and, possibly, the exploitation of this test in the diagnosis of GH hypo-and hypersecretory states (41,42).…”

Section: Time (Min)mentioning

confidence: 99%

“…In recent years, studies in animals (37 -39) and humans (40)(41)(42) have provided evidence that the rebound GH rise which follows SS infusion withdrawal (SSIW) is due, at least in part, to the functional activation of GHRH neurons of the recipient organism. Thus, SSIW may represent a test to indirectly probe endogenous GHRH function, and a potential tool in the diagnosis of GH hyposecretory states (42) or to assess the declining GHRH function in aging (41).…”

Section: Introductionmentioning

confidence: 99%

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Somatostatin infusion withdrawal: studies in the acute and recovery phase of anorexia nervosa, and in obesity

Pincelli¹,

Rigamonti²,

Scacchi³

et al. 2003

European Journal of Endocrinology

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Objective: Changes in GH/IGF-I axis activity occur in both anorexia nervosa (AN) and obesity (OB). A GH hypersecretory state with very low plasma IGF-I levels is present in AN, whereas in morbid OB, GH secretion is dull and plasma IGF-I levels are generally preserved. Endogenous GHRH activity in AN and OB has never been directly studied, although indirect evidence would indicate that GHRH function is altered in either condition, possibly enhanced and reduced respectively. Somatostatin (SS) infusion withdrawal (SSIW) is followed by a rebound rise of plasma GH in animals and humans, an event which, allegedly, is mediated by endogenous GHRH release. Methods: In the present study, 28 young women, eight with active AN (A-AN), six with AN in the recovery phase (R-AN), eight with morbid OB, and six healthy age-matched normal weight subjects (NW), were studied. All subjects underwent, on different occasions, the following two tests: (i) acute GHRH injection (1 mg/kg, i.v.); (ii) infusion of SS (9 mg/kg per h i.v. over 60 min), with blood samples drawn prior to and at different intervals after drug injections. Plasma GH levels were measured at each time interval in all sessions, and, in addition, baseline plasma estradiol, free triiodothyronine, TSH, IGF-I and insulin were measured at 2 30 min. Results: Baseline plasma GH concentrations were significantly higher in A-AN than in NW ð4:7^0:7 vs 2:1^0:6 mg=l; P , 0:01Þ: Baseline GH levels in R-AN were also higher than in NW, but the difference did not reach statistical significance (5:6^1:7 mg=l; not significant (NS)). Baseline plasma GH concentrations were significantly lower in OB than in NW ð0:3^0:1 mg=l; P , 0:01Þ: GHRH-stimulated GH release was significantly higher in A-AN than in NW (mean change in area under the curve (DAUC) 1904:9^626:1 vs 613:9^75:9 mg=l per min, P , 0:01), whereas no statistically significant difference was present between R-AN and NW (mean DAUC 638:2^293:0 mg=l per min, NS); in OB, GHRH failed to evoke a plasma GH rise (mean DAUC 239:8^89:9 mg=l per min vs A-AN, R-AN, and NW, P , 0:01). SS infusion markedly reduced plasma GH concentrations in both A-AN and R-AN and, to a lesser extent, in NW, but failed to do so in OB. In A-AN, SSIW was followed by a plasma GH rise markedly higher than that present in NW (mean DAUC 193:0^42:3 vs 60:1^11:4 mg=l per min, P , 0:01), whereas in R-AN the GH response after SSIW was nearly superimposable on that registered in NW (mean DAUC 72:9^22:8 mg=l per min, NS). There were no changes in plasma GH levels after SSIW in OB (mean DAUC 22:8^9:7 mg=l per min). In all groups, DAUCs of the GH response to GHRH and after SSIW were highly positively correlated ðr ¼ 0:7; P , 0:01Þ: Conclusions: These data support the view that a high endogenous GHRH tone, which subsides in the recovery phase of the disease, is present in AN, whereas GHRH hypofunction, possibly associated with pituitary impairment, might indicate OB.

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Somatostatin Infusion Withdrawal: Studies in Normal Children and in Children with Growth Hormone Deficiency

Cited by 13 publications

References 37 publications

Growth hormone (GH) rebound rise following somatostatin infusion withdrawal: studies in dogs with the use of GH-releasing hormone and a GH-releasing peptide

Growth hormone (GH) rebound rise following somatostatin infusion withdrawal: studies in dogs with the use of GH-releasing hormone and a GH-releasing peptide

Endogenous Estrogen Regulates Somatostatin-Induced Rebound GH Secretion in Postmenopausal Women

Somatostatin infusion withdrawal: studies in the acute and recovery phase of anorexia nervosa, and in obesity

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