Acceleration of Growth Rate in Growth Hormone-Deficient Children Treated with Human Growth Hormone-Releasing Hormone

Mo, Thorner; Rogol, Alan D.; Rm, Blizzard; Gj, Klingensmith; Najjar, Jennifer; Misra, R; Burr, Ian M.; Chao, Gary; Martha, Paul M.; McDonald, Jay A.

doi:10.1203/00006450-198808000-00001

Cited by 61 publications

(20 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This finding is of particular clinical interest, since children with isolated GHD often do not have any alteration in somatotrophs but rather have impaired hypothalamic function causing deregulation in GHRH secretion (16). Indeed, GHRH treatment of these children accelerates growth (6,15), suggesting that GHRH is an ideal and more physiological treatment when GHD is due to hypothalamic dysfunction rather than to primary pituitary disease.…”

Section: Discussionmentioning

confidence: 99%

“…Although daily injection of recombinant human GH is presently the only therapeutic option available for patients with GH deficiency (GHD), GHRH may represent a more valid and physiological approach, especially for children with isolated GHD, in whom this condition seems to be related to altered hypothalamic function rather than to impaired GH secretory capacity (16). However, GHRH has limited therapeutical use in children because of its very short half-life (9), requiring multiple daily injections or infusion by a pump.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse

Alba¹,

Fintini²,

Sagazio³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Although the majority of children with isolated growth hormone (GH) deficiency have a good growth response to GH-releasing hormone (GHRH), the use of this therapeutic agent is limited by its very short half-life. Indeed, we have shown that, in mice with GHRH gene ablation (GHRH knockout; GHRHKO), even twice-daily injections of a GHRH analog are unable to normalize growth. CJC-1295 is a synthetic GHRH analog that selectively and covalently binds to endogenous albumin after injection, thereby extending its half-life and duration of action. We report the effects of CJC-1295 administration in GHRHKO animals. Three groups of 1-wk-old GHRHKO mice were treated for 5 wk with 2 μg of CJC-1295 at intervals of 24, 48, and 72 h. Placebo-treated GHRHKO mice and mice heterozygous for the GHRHKO allele served as controls. GHRHKO animals receiving daily doses of CJC-1295 exhibited normal body weight and length. Mice treated every 48 and 72 h reached higher body weight and length than placebo-treated animals, without full growth normalization. Femur and tibia length remained normal in animals treated every 24 and 48 h. Relative lean mass and subcutaneous fat mass were normal in all treated groups. CJC-1295 caused an increase in total pituitary RNA and GH mRNA, suggesting that proliferation of somatotroph cells had occurred, as confirmed by immunohistochemistry images. These findings demonstrate that treatment with once-daily administration of CJC-1295 is able to maintain normal body composition and growth in GHRHKO mice. The same dose is less effective when administered every 48 or 72 h.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse

Alba¹,

Fintini²,

Sagazio³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…On this basis it was tried to establish its utility as a diagnostic useful tool for clearly defining when a child was GH-deficient (GHD), and even more it was thought that this peptide would allow to define whether the deficiency of GH secretion occurred as a consequence of an hypothalamic dysfunction, or affectation, or it has its origin at the pituitary level [3][4][5][6]. Moreover, it was thought that in the cases of GHD due to a hypothalamic dysfunction the administration of GHRH might replace the treatment with GH [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Clonidine Plus GHRH Administration for Diagnosing Growth Hormone Deficiency in Children

Devesa¹

2017

J Clin Mol Endocrinol

View full text Add to dashboard Cite

Objective: To analyze the effectiveness and reproductivity of a challenge with clonidine (CLO) plus GHRH administration to establish a state of GH-deficiency and the causes of it.Methods: 24 children (17M, 7F) with stature <1 or 2 SD from P3, previously studied with different classical tests, were given CLO (150 µg/m2 orally, at time 0') plus GHRH (60' later, 1 µg/kg, iv). This test was repeated but giving placebo at time 0'. For comparison purposes, 20 agematched normal children (14M, 6F) were studied. Growth velocity (GV) and bone age (BA) before performing CLO +GHRH were considered.Results: While classical GH tests show a great variability of negative or positive GH responses in the same short patient, all but two patients significantly responded to CLO+GHRH (GH peak: 42.2 ± 19 vs. 41.6 ± 3.5 in controls). Controls showed a significant positive correlation between the amplitude of GH response and chronological and bone age (R=0.832; F=37.6; P=0.001, multiple regression analysis): y=a+b × BA+c × CA, where y=GH peak, BA=bone age, CA=chronological age, and a, b and c are constants. This equation allows to establish the value of GH peak theoretically obtained after CLO+GHRH challenge in a normal child. Applying this equation to the responses to CLO+GHRH in short children a deviation, ranging between -435% and +41%, was obtained between theoretical and real GH peaks (%DT-R). Responses between -20% to +20% were considered normal. Plotting these responses (% DT-R) against the SD of the mean of the BA to GV ratio in normal children, five populations were defined: 1) Low response and low GV for BA; 2) Low response and normal GV for BA; 3) Normal response and low GV for BA; 4) Normal response and normal GV for BA; and 5) High response and low GV for BA. Conclusion:The test CLO+GHRH is safe, effective and unique to detect GH-deficiency and its causes in short children and adults.

show abstract

“…From the studies of Thorner et al, it would appear that more often the CNS pathology involves the hypothalamus rather than the pituitary gland. 4,5 It can be expected that mutations of the gene coding for GHRF will be found among a small percentage of patients with IGHD, but to date, none have been described. …”

Section: Growth Hormone Releasing Factor (Ghrf)mentioning

confidence: 99%

“…About half of these patients responded with growth rates that were comparable to those seen in children with IGHD treated with growth hormone. 4 Most patients with IGHD probably do not have a genetic defect as the cause of their dwarfism. Many of these patients are felt to have sustained a variety of CNS insults resulting in IGHD.…”

Section: Growth Hormone Releasing Factor (Ghrf)mentioning

confidence: 99%

The Genetics of the Human Growth Hormone Axis and Associated Dwarfing Disorders

et al. 1996

View full text Add to dashboard Cite

Acceleration of Growth Rate in Growth Hormone-Deficient Children Treated with Human Growth Hormone-Releasing Hormone

Cited by 61 publications

References 10 publications

Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse

Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse

Clonidine Plus GHRH Administration for Diagnosing Growth Hormone Deficiency in Children

The Genetics of the Human Growth Hormone Axis and Associated Dwarfing Disorders

Contact Info

Product

Resources

About