Sequential measurements of IGF-I serum concentrations in adolescents with Laron syndrome treated with recombinant human IGF-I (rhIGF-I)
-
Thomas Breil
,
Carolin Kneppo
Abstract
Background
Recombinant human insulin-like growth factor 1 (rhIGF-I) has been approved as an orphan drug for the treatment of growth failure in children and adolescents with severe primary IGF-I deficiency (SPIGFD) with little pharmacokinetic data available. Therefore, sequential measurements of serum IGF-I, glucose, potassium, insulin and cortisol were performed in patients treated with rhIGF-I to evaluate their significance in safety and efficacy.
Methods
Repetitive blood samples were taken after meals before and 30, 60, 120, 180 and 360 min after rhIGF-I injections in two male patients with Laron syndrome at times of dose adjustments.
Results
Maximal IGF-I concentrations were observed 2 h after injections (495 ng/mL) and concentrations were still higher 6 h after injections than at baseline (303 ng/mL vs. 137 ng/mL). Thirteen percent of all and 33% of maximum IGF-I concentrations were greater than +2 standard deviation score (SDS) calculated for bone age (BA) (IGF-I SDS BA) rather than chronological age (CA) as BA was significantly delayed to CA by 3.2 years (p=0.0007). Height velocities correlated with individual maximum IGF-I SDS BA (ρ=0.735; p<0.0001). Serum insulin, cortisol and glucose did not correlate with IGF-I concentrations, but serum potassium showed a negative correlation (ρ=−0.364; p<0.0001) with IGF-I concentrations.
Conclusions
Sequential measurements of serum IGF-I, glucose and potassium in patients with Laron syndrome may aid in optimizing and individualizing rhIGF-I treatment. IGF-I concentrations should be referenced according to BA which better reflects the biological age. The inverse correlation of IGF-I and serum potassium concentrations after injections of rhIGF-I has not been reported before and warrants further consideration.
Appendix
Collaborators in the German IGF-I Deficiency Study Group: Prof. Dr. Hermann L. Müller (Oldenburg), Dr. Klaus Kapelari (Innsbruck), Dr. Dirk Schnabel (Berlin), and Prof. Dr. Joachim Woelfle (Bonn).
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This study was supported by an unrestricted grant of IPSEN Pharma GmbH, 76275 Ettlingen, Germany. IPSEN Pharma GmbH was not involved in the design, conduct, or analysis of data from this study, nor was it involved with the preparation of the manuscript.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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Article note
This work was presented in part at the 53rd annual meeting of the European Society of Paediatric Endocrinology 2014 in Dublin, the Republic of Ireland.
©2018 Walter de Gruyter GmbH, Berlin/Boston
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Articles in the same Issue
- Frontmatter
- Original Articles
- Urinary bisphenol-A levels in children with type 1 diabetes mellitus
- The relationship between metabolic syndrome, cytokines and physical activity in obese youth with and without Prader-Willi syndrome
- Association of anthropometric measures and cardio-metabolic risk factors in normal-weight children and adolescents: the CASPIAN-V study
- The effect of obesity and insulin resistance on macular choroidal thickness in a pediatric population as assessed by enhanced depth imaging optical coherence tomography
- Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR): clinical heterogeneity and long-term efficacious management of eight patients from four unrelated Arab families with a loss of function VDR mutation
- Long-term thyroid disorders in pediatric survivors of hematopoietic stem cell transplantation after chemotherapy-only conditioning
- Screening for autoimmune thyroiditis and celiac disease in minority children with type 1 diabetes
- Resistance exercise alone improves muscle strength in growth hormone deficient males in the transition phase
- Sequential measurements of IGF-I serum concentrations in adolescents with Laron syndrome treated with recombinant human IGF-I (rhIGF-I)
- Symptomatic Rathke cleft cyst in paediatric patients – clinical presentations, surgical treatment and postoperative outcomes – an analysis of 38 cases
- Molecular genetics of tetrahydrobiopterin deficiency in Chinese patients
- Single center experience of biotinidase deficiency: 259 patients and six novel mutations
- Next-generation sequencing as a second-tier diagnostic test for newborn screening
- Case Reports
- Thyroid storm after choking
- Three new Brazilian cases of 17α-hydroxylase deficiency: clinical, molecular, hormonal, and treatment features
- Diazoxide toxicity in a child with persistent hyperinsulinemic hypoglycemia of infancy: mixed hyperglycemic hyperosmolar coma and ketoacidosis
- Refractory hypoglycemia in a pediatric patient with desmoplastic small round cell tumor
