Somapacitan dose–IGF-I–response and impact of starting dose levels in adults with growth hormone deficiency – a model-based analysis

2020 ◽  
Author(s):  
Kildemoes Rasmus Juul ◽  
Overgaard Rune Viig ◽  
Rasmussen Michael Højby
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Hormone Deficiency ◽  
Model Based ◽  
Starting Dose ◽  
Igf I ◽  
Dose Levels ◽  
Model Based Analysis

scholarly journals Controversies in the diagnosis and management of growth hormone deficiency in childhood and adolescence

2015 ◽  
Vol 101 (1) ◽  
pp. 96-100 ◽  
Author(s):  
P G Murray ◽  
M T Dattani ◽  
P E Clayton
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Hormone Deficiency ◽  
Childhood And Adolescence ◽  
Supporting Evidence ◽  
Diagnosis And Management ◽  
False Positive Diagnosis ◽  
Starting Dose ◽  
Igf I ◽  
Stimulation Tests

Growth hormone deficiency (GHD) is a rare but important cause of short stature in childhood with a prevalence of 1 in 4000. The diagnosis is currently based on an assessment of auxology along with supporting evidence from biochemical and neuroradiological studies. There are significant controversies in the diagnosis and management of GHD. Growth hormone (GH) stimulation tests continue to play a key role in GHD diagnosis but the measured GH concentration can vary significantly with stimulation test and GH assay used, creating difficulties for diagnostic accuracy. Such issues along with the use of adjunct biochemical markers such as IGF-I and IGFBP-3 for the diagnosis of GHD, will be discussed in this review. Additionally, the treatment of GHD remains a source of much debate; there is no consensus on the best mechanism for determining the starting dose of GH in patients with GHD. Weight and prediction based models will be discussed along with different mechanisms for dose adjustment during treatment (auxology or IGF-I targeting approaches). At the end of growth and childhood treatment, many subjects diagnosed with isolated GHD re-test normal. It is not clear if this represents a form of transient GHD or a false positive diagnosis during childhood. Given the difficulties inherent in the diagnosis of GHD, an early reassessment of the diagnosis in those who respond poorly to GH is to be recommended.

Erythrocytes from patients with low serum concentrations of IGF-I have an increase in receptor sites for IGF-I

1991 ◽  
Vol 125 (4) ◽  
pp. 354-358 ◽  
Author(s):  
R. Eshet ◽  
Z. Dux ◽  
A. Silbergeld ◽  
R. Koren ◽  
B. Klinger ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Specific Binding ◽  
Hormone Deficiency ◽  
Scatchard Analysis ◽  
Isolated Growth Hormone Deficiency ◽  
Receptor Sites ◽  
Igf I ◽  
The Mean ◽  
Low Serum

Abstract. The binding characteristics of insulin-like growth factor I on erythrocytes were studied in 11 patients with long-term IGF-I deprivation and low serum IGF-I levels. Six patients had Laron type dwarfism and 5 idiopathic isolated growth hormone deficiency, with a mean (± sem) serum IGF-I level of 6.01±1.01 nmol/l as compared with that in 25 normal controls of 26.35±2.73 nmol/l (p=0.00001). The mean (± sem) [125I]IGF-I specific binding at a concentration of 4×1012 cell/l was 12.11±1.29% for the patient group compared with 8.75±0.62% for the controls (p=0.005). Scatchard analysis showed a curvilinear plot. Using a non-linear curve fit, the mean (± sem) number of high-affinity receptor sites per cell was found to be 7.34±1.80 in the IGF-I-deprived patients and 2.84±0.29 in the controls (p=0.0005). The mean ± sem dissociation constant was found to be 0.33±0.10 nmol/l for the patients and 0.26±0.08 nmol/l for the controls (NS). This study has demonstrated that the low serum concentration of IGF-I in Laron type dwarfism and isolated growth hormone deficiency is associated with an increase in receptor sites for IGF-I on the erythrocytes. The application of this property as a diagnostic aid remains to be established.

Growth hormone and insulin-like growth factor regulate insulin-like growth factor-binding protein-1 in Laron type dwarfism, growth hormone deficiency and constitutional short stature

1992 ◽  
Vol 127 (4) ◽  
pp. 351-358 ◽  
Author(s):  
Zvi Laron ◽  
Anne-Maria Suikkari ◽  
Beatrice Klinger ◽  
Aviva Silbergeld ◽  
Athalia Pertzelan ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Growth Hormone Deficiency ◽  
Short Stature ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Healthy Children ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Igf I

Insulin-like growth factors (IGFs) mediate the effects of growth hormone (GH), and the insulin-like growth factor-binding proteins (IGFBPs) modulate the actions of IGFs in tissues. We studied the circulating levels of IGFBP-1 in 6 children and 9 adults with Laron type dwarfism (LTD), in 11 children and 21 adults with growth hormone deficiency (GHD), and in 8 children with constitutional short stature. Compared with the situation in healthy children, the basal serum IGFBP-1 concentration was 5.4-fold higher in LTD children, 4.1-fold higher in GHD children, and 3.8-fold higher in children with short stature (p<0.02 vs controls in all groups). In adult patients with multiple pituitary hormone deficiency (MPHD), the IGFBP-1 concentration was 2-fold elevated, but it was normal in adult LTD patients. Intravenous (N= 10) or subcutaneous (N=9) administration ofIGF-I (75 μg·kg−1 and 150 μg·kg−1, respectively) in LTD children resulted in a rapid 50–60% fall in serum insulin (p<0.02), a decline in blood glucose and a concomitant 40–60% rise of IGFBP-1 levels (p<0.05). Treatment for seven days with IGF-I (150 μg·kg−1·d−1) resulted in a decrease by 34% and 44% of serum IGFBP-1 level in two out of three children with LTD. After prolonged GH therapy, the IGFBP-1 level fell in GHD children by 29% (p<0.05), in GHD adults by 52% (p<0.02) and in children with constitutional short stature by 17% (p<0.02). IGFBP-1 and insulin concentrations were inversely related in patients with GHD (r= −0.66, p<0.001) or with LTD (r= −0.57, p<0.05). Our data suggest that: (a) increased IGFBP-1 concentration in LTD, GHD and constitutional short children may, at least in part, be accounted for by an IGF-I deficiency; (b) both the rise in IGF-I and a fall in insulin contributed to the rise in IGFBP-1 after acute IGF-I administration; (c) prolonged IGF-I or GH treatment causes a persistent decline in IGFBP-1 concentration. In conclusion, IGF-I and GH may regulate IGFBP-1 secretion either directly or via insulin.

ITT and IGF-I in the diagnosis of growth hormone deficiency in adults

The Lancet ◽  
1994 ◽  
Vol 344 (8922) ◽  
pp. 613-614 ◽  
Author(s):  
DavidM. Hoffman ◽  
TuanV. Nguyen ◽  
AnthonyJ. O'Sullivan ◽  
RobertC. Baxter ◽  
KenK.Y. Ho
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Hormone Deficiency ◽  
Igf I

New approach to the diagnosis of growth hormone deficiency in adults

1996 ◽  
Vol 134 (3) ◽  
pp. 352-356 ◽  
Author(s):  
Ezio Ghigo ◽  
Gianluca Aimaretti ◽  
Laura Gianotti ◽  
Jaele Bellone ◽  
Emanuela Arvat ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Gh Deficiency ◽  
Serum Insulin ◽  
Normal Subjects ◽  
Hormone Deficiency ◽  
New Approach ◽  
Igf I ◽  
Ghrh Test ◽  
Gh Deficiency In Adults

Ghigo E, Aimaretti G, Gianotti L, Bellone J, Arvat E, Camanni F. New approach to the diagnosis of growth hormone deficiency in adults. Eur J Endocrinol 1996;134:352–6. ISSN 0804–4643 Pyridostigmine (PD), a muscarinic cholinergic agonist, and arginine (ARG) clearly increase the growth hormone (GH) response to growth hormone-releasing hormone (GHRH) in man. The current study was undertaken to investigate the value and safety of PD + GHRH and ARG + GHRH tests as well as the measurement of serum insulin-like growth factor I (IGF-I) in diagnosing GH deficiency in adults. Fifty-four patients considered GH deficient from extensive organic or idiopathic pituitary disease and 326 healthy adults were studied. The IGF-I concentrations were lower than the 3rd percentile of normal values in only 31 of the 54 (57.4%) patients with hypopituitarism. However, the IGF-I levels in hypopituitary patients and in normal subjects overlapped more frequently between 41 and 60 years (50%) and between 61 and 80 years (92.3%) as opposed to between 20 and 40 years (8.6%). In contrast to the IGF-I measurement, the ranges of peak GH responses to PD + GHRH and ARG + GHRH tests were clearly differentiated between the hypopituitary (0.2–6.8 and 0.1–9.5 μg/l, respectively) and normal subjects 17.7–114 and 16.1–119 μg/l, respectively). However, the PD + GHRH test was reliable only in subjects of 20–40 years of age. In conclusion, IGF-I measurement had no value in the diagnosis of GH deficiency in adults aged over 40 years, but is reliable enough when young adults of 20–40 years of age are considered. Both PD + GHRH and ARG + GHRH testing should be considered more reliable biochemical measurements of GH deficiency. In contrast to the PD + GHRH test, the ARG + GHRH test is reliable throughout the adult lifespan and appears to be the most appropriate for patient compliance and safety. F Camanni, Divisione di Endocrinologia, Ospedale Molinette, C.so Dogliotti 14, 10126 Torino, Italy

scholarly journals Factors affecting IGF-I level and correlation with growth response during growth hormone treatment in LG Growth Study

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0252283
Author(s):  
Ji Hyun Kim ◽  
Su Jin Kim ◽  
Jieun Lee ◽  
Choong Ho Shin ◽  
Ji-Young Seo
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Growth Response ◽  
Growth Hormone Treatment ◽  
Hormone Treatment ◽  
Hormone Deficiency ◽  
Growth Study ◽  
Korean Children ◽  
Factors Affecting ◽  
Igf I

Growth hormone treatment strategies to achieve the goal include the titration of GH doses according to serum insulin-like growth factor I (IGF-I) concentrations. However, IGF-I levels do not always correlate well with the growth response. This study aims to identify the factors affecting the IGF-I concentration and identify the relationship between IGF-I and the treatment response. The data of prepubertal children treated with recombinant human GH for more than one year were obtained from the LG Growth Study (LGS) Database. This study includes patients with idiopathic growth hormone deficiency (IGHD), organic growth hormone deficiency (OGHD), or Turner syndrome (TS) or small for gestational age (SGA). Among 2,021 participants registered in LGS, 366 subjects were selected, 252 had IGHD, 16 had OGHD, 31 had TS, and 67 were SGA. In the IGHD and SGA groups, IGF-I levels had a positive correlation with weight SDS. There was no significant relationship between the pre-treatment IGF-I level and growth response. However, in the IGHD group, the growth response was significantly higher when the change in the IGF-I SDS value was 1 or more (p = 0.0013). Therefore, IGF-I concentrations should be used as an indicator to monitor the treatment compliance rather than for efficacy determination in Korean children of short stature with GH treatment.

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